EP1317529A1 - Crystal structure of pantothenate synthetase - Google Patents

Abstract

A crystal of pantothenate synthetase (PS) has a monoclinic space group P21 and unit cell dimensions of a = 66.0±0.2Å, b = 78.1±0.2Å, c = 77.1±0.2Å and β = 103.7±0.2°.

Description

CRYSTAL STRUCTURE OF PANTOTHENATE SYNTHETASE

Field of the Invention

The present invention relates to the enzyme pantothenate synthetase, and in particular its crystal structure and the use of this structure in drug discovery.

Background of the Invention

Pantothenic acid (vitamin B₅) is found in coenzyme A (CoA) and the acyl carrier protei ^• (ACP) , both of which are involved in fatty acid metabolism.

Pantothenic acid can be synthesised by plants and microorganisms but animals are apparently unable to make the vitamin, and require it in their diet. However, all organisms are able to convert pantothenic acid to its metabolically active form, coenzyme A.

The pathway for the synthesis of pantothenic acid is shown in Fig. 1. It provides a potential target for the treatment of infectious disease, since inhibitors of the pathway should be damaging to bacteria and fungi but not to human or animal subjects infected by bacteria.

Of specific interest is pantothenate synthetase (D-pantoate: β-alanine ligase (AMP-forming) ; EC 6.3.2.1). This enzyme catalyses the condensation between β-alanine and pantoic acid, the final steps in pantothenic acid biosynthesis. Inhibitors (whether competitive, non-competitive, uncompetitive or irreversible) of pantothenate synthetase would be of significant technical and commercial interest. Purification of pantothenate synthetase (PS) to homogeneity was achieved by Miyatake et. al, (J. Biochem . , 79, (1976), 673-678) . The enzyme was reported to require stoichiometric amounts of ATP as an energy source which is hydrolysed to AMP and inorganic pyrophosphate. The mechanism of the enzymic reaction involves pantoate adenylate as an intermediate.

However, until now no one has successfully determined the structure of PS. This has prevented PS inhibitors being developed via structure-based drug design methodologies.

Knowledge of the structure of PS would significantly assist the rational design of novel therapeutics based on PS inhibitors .

Summary of the Invention

The present invention is at least partly based on overcoming several technical hurdles: we have (i) produced PS crystals of suitable quality, including crystals of selenium atom PS derivatives, for performing X-ray diffraction analyses, (ii) collected X-ray diffraction data from the crystals, (iii) determined a high resolution three-dimensional X-ray crystal structure of PS (i.e. a structure having a resolution which is numerically lower than 2 A) , and (iv) identified sites on the enzyme which are likely to be involved in the enzymic reaction.

In general aspects, the present invention is concerned with identifying or obtaining agent compounds (especially inhibitors of PS) for modulating PS activity, and in preferred embodiments identifying or obtaining actual agent compounds/inhibitors. Crystal structure information presented herein is useful in designing potential inhibitors and modelling them or their potential interaction with the PS binding cavity. Potential inhibitors may be brought into contact with PS to test for ability to interact with the PS binding cavity. Actual inhibitors may be identified from among potential inhibitors synthesized following design and model work performed in silico . An inhibitor identified using the present invention may be formulated into a composition, for instance a composition comprising a pharmaceutically acceptable excipient, and may be used in the manufacture of a medicament for use in a method of treatment. These and other aspects and embodiments of the present invention are discussed below.

In a first aspect, the present invention provides a crystal of PS having a monoclinic space group P2ι, and unit cell dimensions of a = 66.0+0.2A, b = 78.1+0.2A, c = 77.1±0.2A and β = 103.7+0.2°. Preferably the PS is a dimer.

In a further aspect, the invention also provides a crystal of PS having the three dimensional atomic coordinates of Table 1. An advantageous feature of the structure defined by the atomic coordinates is that it has a high resolution, of about 1.7A.

The coordinates of Table 1 provide a measure of atomic location in Angstroms, to a third decimal place. The coordinates are a relative set of positions that define a shape in three dimensions, but the skilled person would understand that an entirely different set of coordinates having a different origin and/or axes could define a similar or identical shape. Furthermore, the skilled person would understand that varying the relative atomic positions of the atoms of the structure so that the root mean square deviation of the residue backbone atoms (i.e. the nitrogen-carbon-carbon backbone atoms of the protein amino acid residues) is less than 1.5 A (preferably less than 1.0 A and more preferably less than 0.5 A) when superimposed on the coordinates provided in Table 1 for the residue backbone atoms, will generally result in a structure which is substantially the same as the structure of Table 1 in terms of both its structural characteristics and potency for structure-based design of PS inhibitors. Likewise the skilled person would understand that changing the number and/or positions of the water molecules and/or substrate molecules of Table 1 will not generally affect the potency of the structure for structure-based design of PS inhibitors. Thus for the purposes described herein as being aspects of the present invention, it is within the scope of the invention if: the Table 1 coordinates are transposed to a different origin and/or axes; the relative atomic positions of the atoms of the structure are varied so that the root mean square deviation of residue backbone atoms is less than 1.5 A (preferably less than 1.0 A and more preferably less than 0.5 A) when superimposed on the coordinates provided in Table 1 for the residue backbone atoms; and/or the number and/or positions of water molecules and/or substrate molecules is varied. Reference herein to the coordinate data of Table 1 thus includes the coordinate data in which one or more individual values of the Table are varied in this way. By "root mean square deviation" we mean the square root of the arithmetic mean of the squares of the deviations from the mean.

Thus, for example, varying the atomic positions of the atoms of the structure by up to about 0.2 A in any direction will result in a structure which is substantially the same as the structure of Table 1 in terms of both its structural characteristics and utility e.g. for structure-based drug design.

The provision of the high resolution structure of Table 1 provides those of skill in the art with a detailed insight into the mechanisms of action of PS. This insight provides a means to design new antibacterial agents which have the potential to inhibit the process of pantothenate synthesis in bacteria and fungi, or to modulate the activity of the enzyme, for example such that the enzyme works more effectively on prodrugs which are converted by PS into an antibacterial drug.

In a further aspect, the invention provides a method for crystallizing a selenium atom PS derivative which comprises producing PS by recombinant production in a bacterial host (e.g. E . coli ) in the presence of selenomethionine, recovering a selenium atom PS derivative from the host and growing crystals from the recovered selenium atom PS derivative.

Thus, the selenium atom PS derivative and PS produced by crystallising native PS (see the detailed description below) are provided as crystallised proteins suitable for X-ray diffraction analysis.

The crystals may be grown by any suitable method, e.g. the hanging drop method.

The above aspects of the invention, both singly and in combination, all contribute to features of the invention which are advantageous .

The provision of the crystal structure of PS allows a novel approach for drug discovery for modulators of this enzyme. Accordingly, the invention provides a computer-based method of rational drug design which comprises: providing the structure of the PS as defined by the coordinates of Table 1; providing the structure of a candidate modulator molecule; and fitting the structure of the candidate modulator molecule to the structure of the PS of Table 1.

In an alternative aspect, the method of the invention may utilise the coordinates of atoms of interest of the PS which are in the vicinity of a putative substrate and/or co-factor binding regions in order to model the pocket in which the substrate or co-factor binds. These coordinates may be used to define a space which is then screened "in silico" against a candidate modulator molecule. Thus the invention provides a computer-based method of rational drug design which comprises: providing the coordinates of at least two atoms of the PS of Table 1 ("selected coordinates") ; providing the structure of a candidate modulator molecule; and fitting the structure of the candidate modulator molecule to the selected coordinates of the PS.

In practice, it will be desirable to model a sufficient number of atoms of the PS as defined by the coordinates of Table 1 which represent a binding pocket. Binding pockets and other features of the interaction of PS with co-factor are described in the detailed description. Thus, in this embodiment of the invention, there will preferably be provided the coordinates of at least 5, preferably at least 10, more preferably at least 50 and even more preferably at least 100 selected atoms of the PS structure.

Our structure of PS has allowed us to identify particular sites of interaction of Mg²⁺, ATP, pantoate and β-alanine. The selected coordinates preferably include at least one of the coordinates defining these particular sites. Residues providing some of these sites include Pro28, Met30, His34, Asp35, Gly36, His37, Leu40, Asn58, Glnδl, Phe62, Tyr71, Argl23, Hisl26, Ilel33, Vall34, Leul37, Lysl51, Glnl55, Metl78, Alal85, Leul86, Serl87, Serl88, and Argl89.

As discussed in the detailed description, we believe that ATP interacts with one or more of Met30, His34, Asp35, Gly36, His37, Leu40, Lysl51, Metl78, Alal85, Leul86, Serl87, Serl88, and Argl89; Mg²⁺ interacts with either or both of Tyr71 and Serl88; pantoate interacts with one or more of Pro28, Met30, Asn58, Glnδl, Ilel33, Vall34, Leul37, and Glnl55; and β-alanine interacts with one or more of Met30, Phe62, Tyr71, Argl23, and Hisl26.

In another aspect, the method of the invention may utilise a sub- domain of interest of the PS which is in the vicinity of a region which binds substrate or co-factor. Thus, the invention provides a computer-based method of rational drug design which comprises: providing the coordinates of at least a sub-domain of the PS; providing the structure of a candidate modulator molecule; and fitting the structure of the candidate modulator molecule to the coordinates of the PS sub-domain provided.

Brief Description of the Drawings

Fig. 1 shows schematically the pathway for the synthesis of pantothenic acid,

Figs. 2a-c show the general structure of PS, being respectively (a) a "cartoon" of the dimer, (b) a schematic diagram of the monomer topology with numbering of secondary structures, and (c) a schematic plot of hydrogen bonding patterns between secondary structures,

Fig. 3 is a stereo pair of images showing schematically the core of the dimerisation interface, and Fig. 4 shows a Connolly surface generated around the proposed PS active sites.

Detailed Description of the Invention

By "fitting", it is meant determining by automatic, or semiautomatic means, interactions between at least one atom of the candidate and at least one atom of the PS, and calculating the extent to which such an interaction is stable. Interactions include attraction and repulsion, brought about by charge, steric considerations and the like. Various computer-based methods for fitting are described further herein.

By "sub-domain" is meant at least one (e.g. one, two, three or four) complete element (s) of secondary structure, i.e. an alpha helix or a beta sheet, as described in the detailed description below.

Table 1 gives atomic coordinate data for PS (which we have crystallised as a dimer) and associated water molecules. In Table 1 "Atom type" refers to the respective element, the first letter defining the element; "X, Y, Z" define, with respect to the crystallographic axes, the atomic position (in A) of the respective atom; "Occ. " is the occupancy of the atom in the respective position; and "B" is a temperature factor (in A²) which accounts for movement of the atom around its atomic centre.

Particular regions of the PS include those identified as putative substrate or cofactor binding regions based on the data provided in Table 1.

As indicated above, modulators of PS may be inhibitors of the enzyme or compounds which affect its specificity or activity in relation to pantoate in other ways. The invention is particularly suitable for the design, screening and development of PS inhibitor components. It is thus a preferred aspect of the invention that modulators are inhibitors .

The step of providing the structure of a candidate modulator molecule may involve selecting the compound by computationally screening a database of compounds for interaction with the active site. For example, a 3-D descriptor for the potential modulator may be derived, the descriptor including geometric and functional constraints derived from the architecture and chemical nature of the active site. The descriptor may then be used to interrogate the compound database, a potential modulator being a compound that has a good match to the features of the descriptor. In effect, the descriptor is a type of virtual pharmacophore .

In any event, the determination of the three-dimensional structure of PS provides a basis for the design of new and specific ligands for PS. For example, knowing the three- dimensional structure of PS, computer modelling programs may be used to design different molecules expected to interact with possible or confirmed active sites, such as binding sites or other structural or functional features of PS.

More specifically, a potential modulator of PS activity can be examined through the use of computer modelling using a docking program such as GRAM, DOCK, or AUTODOCK (see Walters et al., Drug Discovery Today, Vol.3, No. , (1998), 160-178, and Dunbrack et al., Folding and Design, 2, (1997), 27-42) to identify potential inhibitors of PS. This procedure can include computer fitting of potential inhibitors to PS to ascertain how well the shape and the chemical structure of the potential inhibitor will bind to the enzyme. Also computer-assisted, manual examination of the active site structure of PS may be performed. The use of programs such as GRID (Goodford, J. Med. Chem . , 28, (1985), 849-857) - a program that determines probable interaction sites between molecules with various functional groups and the enzyme surface - may also be used to analyse the active site to predict partial structures of inhibiting compounds.

Computer programs can be employed to estimate the attraction, repulsion, and steric hindrance of the two binding partners (e.g. the PS and a potential inhibitor). Generally the tighter the fit, the fewer the steric hindrances, and the greater the attractive forces, the more potent the potential modulator, since these properties are consistent with a tighter binding constant. Furthermore, the more specificity in the design of a potential drug, the more likely it is that the drug will not interact with other proteins as well. This will tend to minimise potential side-effects due to unwanted interactions with other proteins.

In a further aspect, the present invention provides a method for identifying a candidate modulator (e.g. potential inhibitor) of PS comprising the steps of: employing a three-dimensional structure of PS, or at least one sub-domain thereof, to characterise at least one PS active site, the three-dimensional structure being defined by atomic coordinate data according to Table 1; and identifying the candidate modulator by designing or selecting a compound for interaction with the active site.

If more than one PS active site is characterised and a plurality of respective compounds are designed or selected, the modulator may formed by linking the respective compounds into a larger compound which maintains the relative positions and orientations of the respective compounds at the active sites. The larger compound may be formed as a real molecule or by computer modelling.

The step of identifying the candidate modulator may involve selecting the compound by computationally screening a database of compounds for interaction with the active site.

In another aspect, in place of in silico methods, high throughput screening of compounds to select compounds with binding activity may be undertaken, and those compounds which show binding activity may be selected as possible candidate modulators, and further crystallized with PS (e.g. by co- crystallization or by soaking) for X-ray analysis. The resulting X-ray structure may be compared with that of Table 1 for a variety of purposes. For example, where the contacts made by such compounds overlap with those may by pantoate, novel molecules comprising residues which contain contacts of both pantoate and the other compound may be provided.

Having designed or selected possible binding candidate modulators by determining those which have favourable fitting properties (e.g. strong attraction between candidate and PS), these can then be screened for activity. Consequently, the method preferably further comprises the steps of: obtaining or synthesising the candidate modulator; and contacting the candidate modulator with PS to determine the ability of the candidate modulator to interact with PS.

More preferably, in the latter step the candidate modulator is contacted with PS under conditions to determine its function.

For example, in the contacting step above the candidate modulator is contacted with PS in the presence of a substrate, and typically a buffer, to determine the ability of said candidate modulator to inhibit PS. The substrate may be e.g. pantoic acid (or a salt thereof) , β-alanine (or a salt thereof), or ATP. So., for example, an assay mixture for PS may be produced which comprises the candidate modulator, substrate and buffer.

Instead of, or in addition to, performing such an assay, the method may comprise the further steps of: obtaining or synthesising said candidate modulator; forming a complex of PS and said candidate modulator; and analysing said complex by X-ray crystallography to determine the ability of said candidate modulator to interact with PS. Detailed structural information can then be obtained about the binding of the candidate modulator to PS, and in the light of this information adjustments can be made to the structure or functionality of the candidate modulator, e.g. to improve binding to the active site. The above steps may be repeated and re-repeated as necessary.

In another aspect, the invention relates to a method of determining three dimensional structures of PS homologues of unknown structure by utilising the structural coordinates of Table 1.

For example, if X-ray crystallographic or NMR spectroscopic data is provided for a PS homologue of unknown structure, the structure of PS as defined by Table 1 may be used to interpret that data to provide a likely structure for the PS homologue by techniques which are well known in the art, e.g. phase modelling in the case of X-ray crystallography.

One embodiment of the method comprises the steps of: (a) aligning a representation of an amino acid sequence of a PS homologue of unknown structure with the amino acid sequence of PS to match homologous regions of the amino acid sequences; (b) modelling the structure of the matched homologous regions of the PS of unknown structure on the structure as defined by Table 1 of the corresponding regions of PS; and

(c) determining a conformation (e.g. so that favourable interactions are formed within the PS of unknown structure and/or so that a low energy conformation is formed) for the PS of unknown structure which substantially preserves the structure of said matched homologous regions.

The term "homologous regions" describes amino acid residues in two sequences that are identical or have similar (e.g. aliphatic, aromatic, polar, negatively charged, or positively charged) side-chain chemical groups. Identical and similar residues in homologous regions are sometimes described as being respectively "invariant" and "conserved" by those skilled in the art.

Preferably one or all of steps (a) to (c) are performed by computer modelling. Homology modelling is a technique that is well known to those skilled in the art (see e.g. Greer, Science, Vol. 228, (1985), 1055, and Blundell et al . , Eur . J. Bioche , Vol. 172, (1988), 513).

In general, comparison of amino acid sequences is accomplished by aligning the amino acid sequence of a polypeptide of a known structure with the amino acid sequence of the polypeptide of unknown structure. Amino acids in the sequences are then compared and groups of amino acids that are homologous are grouped together. This method detects conserved regions of the polypeptides and accounts for amino acid insertions or deletions.

Homology between amino acid sequences can be determined using commercially available algorithms. The programs BLAST, gapped BLAST, BLASTN and PSI-BLAST (provided by the National Center for Biotechnology Information) are widely used in the art for this purpose, and can align homologous regions of two amino acid sequences.

Once the amino acid sequences of the polypeptides with known and unknown structures are aligned, the structures of the conserved amino acids in a computer representation of the polypeptide with known structure are transferred to the corresponding amino acids of the polypeptide whose structure is unknown. For example, a tyrosine in the amino acid sequence of known structure may be replaced by a phenylalanine, the corresponding homologous amino acid in the amino acid sequence of unknown structure.

The structures of amino acids located in non-conserved regions may be assigned manually by using standard peptide geometries or by molecular simulation techniques, such as molecular dynamics. The final step in the process is accomplished by refining the entire structure using molecular dynamics and/or energy minimization.

The aspects of the invention described herein which utilise the PS structure in silico may be equally applied to homologue models of PS obtained by the above aspect of the invention, and this application forms a further aspect of the present invention. Thus having determined a conformation of a PS by the method described above, such a conformation may be used in a computer-based method of rational drug design as described herein. In another aspect, the invention includes a compound which is identified as a modulator (preferably an inhibitor) of PS by the methods of the invention described above.

Following identification of an inhibitor compound, it may be manufactured and/or used in the preparation, i.e. manufacture or formulation, of a composition such as a medicament, pharmaceutical composition or drug. These may be administered to individuals.

Thus, the present invention extends in various aspects not only to an inhibitor as provided by the invention, but also a pharmaceutical composition, medicament, drug or other composition comprising such an inhibitor e.g. for treatment

(which may include preventative treatment) of disease such as microbial infection; a method comprising administration of such a composition to a patient, e.g. for treatment of disease such as microbial infection; use of such an inhibitor in the manufacture of a composition for administration, e.g. for treatment of disease such as microbial infection; and a method of making a pharmaceutical composition comprising admixing such an inhibitor with a pharmaceutically acceptable excipient, vehicle or carrier, and optionally other ingredients.

In a further aspect, the invention provides a method for determining the structure of a modulator of PS bound to PS, said method comprising: providing a crystal of PS according to the invention; soaking the crystal with said modulator; and determining the structure of said PS-modulator complex.

Alternatively, the PS and modulator may be co-crystallized. In either case, pantoate, β-alanine and/or pantothenate or an analogue thereof may optionally be present.

Having obtained and characterized a modulator compound according to the invention, the invention further provides a method for modulating the activity of PS which method comprises : providing PS under conditions where, in the absence of modulator, the PS is able to synthesize pantothenate from pantoate; providing a modulator compound; and determining the extent to which the activity of PS is altered by the presence of said compound.

In another aspect, the present invention provides systems, particularly a computer system, intended to generate structures and/or perform rational drug design for PS or a complex of PS and a potential modulator, the systems containing either (a) atomic coordinate data according to Table 1, said data defining the three-dimensional structure of PS or at least one sub-domain thereof, or (b) structure factor data for PS, said structure factor data being derivable from the atomic coordinate data of Table 1.

In a further aspect, the present invention provides computer readable media with either (a) atomic coordinate data according to Table 1 recorded thereon, said data defining the three-dimensional structure of PS, at least one atom or at least one sub-domain thereof, or (b) structure factor data for PS recorded thereon, the structure factor data being derivable from the atomic coordinate data of Table 1.

As used herein, "computer readable media" refers to any medium or media which can be read and accessed directly by a computer. Such media include, but are not limited to: magnetic storage media such as floppy discs, hard disc storage medium and magnetic tape; optical storage media such as optical discs or CD-ROM; electrical storage media such as RAM and ROM; and hybrids of these categories such as magnetic/optical storage media.

By providing such computer readable media, the atomic coordinate data can be routinely accessed to model PS or a sub-domain thereof. For example, RASMOL (Sayle et al . , TIBS, Vol. 20, (1995), 374) is a publicly available computer software package which allows access and analysis of atomic coordinate data for structure determination and/or rational drug design.

On the other hand, structure factor data, which are derivable from atomic coordinate data (see e.g. Blundell et al . , in Protein Crystallography, Academic Press, New York, London and San Francisco, (1976) ) , are particularly useful for calculating e.g. difference Fourier electron density maps.

As used herein, "a computer system" refers to the hardware means, software means and data storage means used to analyse the atomic coordinate data of the present invention. The minimum hardware means of the computer-based systems of the present invention comprises a central processing unit (CPU) , input means, output means and data storage means. Desirably a monitor is provided to visualise structure data. The data storage means may be RAM or means for accessing computer readable media of the sixth aspect of the invention. Examples of such systems are microcomputer workstations available from Silicon Graphics Incorporated and Sun Microsystems running Unix based, Windows NT or IBM OS/2 operating systems. In a further aspect, the invention provides a method of analysing a complex of PS and a potential modulator comprising the step of employing (i) X-ray crystallographic diffraction data from the complex and (ii) a three-dimensional structure of PS, or at least one sub-domain thereof, to generate a difference Fourier electron density map of the complex, the three-dimensional structure being defined by atomic coordinate data according to Table 1. The difference Fourier electron density map may then be analysed.

-Therefore, such complexes can be crystallised and analysed using X-ray diffraction methods, e.g. according to the approach described by Greer et al., J. or^" Medicinal Chemistry, Vol. 37, (1994), 1035-1054, and difference Fourier electron density maps can be calculated based on X-ray diffraction patterns of soaked or co-crystallised PS and the solved structure of uncomplexed PS. These maps can then be analysed e.g. to determine whether and where a particular ligand binds to PS and/or changes the conformation of PS.

Electron density maps can be calculated using programs such as those from the CCP4 computing package (Collaborative Computational Project 4. The CCP4 Suite: Programs for Protein Crystallography, Acta Crystallographies, D50, (1994), 760- 763.) . For map visualisation and model building programs such as "0" (Jones et al., Acta Crystallograhy, A47, (1991), 110- 119) can be used.

PS Structural Characterization

We have found that the structure of a PS monomer consists of two major domains, joined at about residue 176 (Figs. 2a-c) . Domain N (so called because it contains the N terminal) has an alpha-beta-alpha architecture; six parallel β-strands with 1'- 3-2-1-4-5 topology alternate with -helices to form a Rossman fold with central β-sheet sandwiched between two layers of α- helices (Fig. 2b). The helices (αl',1, 2, 3 and 4) pack against the β-sheet in a right-handed way. The secondary structural elements have been numbered in Figs. 2a and b, with elements that are insertions or additions to the "standard" nucleotide-binding Rossman fold (discussed below under "Identification of Likely Active Sites") denoted by primes. Strand β5 leads directly into the short β-hairpin and 3ιo helix motif (β6, β7 and ει₀7), which lies at the head of domain C (containing the C terminal) and is likely to be involved in phosphate binding (see below) . The rest of the domain has a simple two-layer organisation: a helix-turn-helix layered above a flat sheet of three anti-parallel β-strands (α8 and 9, βl0-12) . This sheet faces a prominent cleft in domain N, the predicted catalytic region (see below), making the whole structure resemble somewhat a pot (domain N) with its lid (domain C) on a hinge, a common arrangement in two-domain enzymes .

We have also found that the two monomers, A and B, of PS are related by a non-crystallographic quasi 2-fold rotational symmetry (NCS) axis. The dimerisation interface has a surface area of 1340 A² and the core of the interface is shown in Fig. 3. The centre of the nearly symmetrical dimerisation interface is unusual: below a 2-strand β-sheet (βD from A and B) Vall09, Metl66 and Phel68 form a hydrophobic pocket around weakly H-bonded polar clusters of Serl35, conserved Asnl39 and three water molecules, one of which lies on the NCS axis. Above the β-sheet TyrlOδ, AspllO and Argl28 form a tight charged cluster, and the rest of the interface consists of salt bridges (HislOδ to Aspl65; Argil to Aspl69) and extensive water-mediated H-bonding interactions. The average B-factor of monomer B is about 4 A² greater than that of A, which on the whole contains fewer disordered stretches. Also conformational differences between the monomers which can be explained by crystal packing arrangements are found at residues 173-180 and 187-193.

For residues B187-193, electron density was poor, and the apparent backbone connectivity could not be reconciled with stereochemical and Ramachandran constraints . The loop was eventually modelled using the same residues from monomer A (which are well ordered) , and transformed by the operation that superimposes domain C of monomer A onto monomer B. However, it is likely that residues A187-193 are only ordered because the bottom of the dimerisation region is crystallographically packed tightly against this region and that the disordered seen in B is more realistic for the apo- enzyme in vivo .

Residues 239-244 also have entirely different but defined backbone conformations in the two monomers, and this difference is not readily explained by crystal packing. However, there appears to be no functional significance in the anomaly.

Solving the PS Crystal Structure

To solve the PS crystal structure, molecular replacement was not possible because prior to our determination of the PS structure similarities between the amino acid sequence of E. coli PS and that of proteins with known structures were not evident. Therefore, phase information needed to be obtained ah initio.

The phase problem was first approached by the Multiple Isomorphous Replacement technique, and crystals of PS were soaked with a range of heavy atom salts at a range of concentrations. However, the majority of these conditions resulted in crystal damage.

Eventually, production of selenomethionine PS (SeMet PS) was attempted, the selenium atoms being introduced into the protein prior to crystallisation by recombinant production of the protein in the presence of L-selenomethionine . This was successfully accomplished and is discussed in more detail below. X-ray analysis was performed on PS and SeMet PS crystals .

Production and purification of PS

Native PS

DNA encoding the PanC gene was engineered into a pUC19 expression vector. E.coli cells were transformed using the plasmid.

Colonies of transformed cells were inoculated directly into LB medium containing ampicillin (100 mg/ml) and IPTG (70mg/ml) ; induction of expression was continuous. The cultures were shaken (200 rpm on an orbital shaker) overnight at 37^°C, when the cells were retrieved by centrifugation of the culture medium and the cell pellet stored frozen at -80 C.

Selenomethionine PS

The same E. coli strain was used as for native expression, but the methionine pathway inhibition system (see van Duyne et al., J. Mol . Biol . , 229, (1993), 105-124) was used for selenomethionine incorporation. Cells were grown on a minimal, defined medium (see Table 2) containing selenomethionine as well as six other amino acids, whose presence inhibits the natural pathways for methionine synthesis. A starter culture (100ml) of the same medium as above, but without selenomethionine or the inhibitory amino acids, was inoculated with transformed cells and grown at 37 C to log growth phase. 1ml of this culture was used to inoculate baffled 2/Erlemeyer flasks (250ml complete medium per flask) which were shaken at 37°C overnight and harvested as for native protein.

Purification

Harvested cells were suspended in 20-40ml TD buffer (50mM Tris/HCl pH 7.5 + 0. ImM dithiothreitol) sonicated at maximum intensity for 8 times 15 seconds, with 15 second breaks, and cell debris removed by centrifugation (30 minutes, 15000x g) .

The supernatant was stirred at 4 C while (NH₄)₂S04 was added slowly over ca. 15 minutes to a final concentration of 29.1% (w/v) ; after a further 30 minutes of stirring, precipitated contaminants were removed by centrifugation (30 minutes, 15000x g) . The solution was dialysed overnight against TD buffer (at least 21) .

The dialysed protein solution was loaded at 4^°C onto an anion exchange column (Pharmacia Q-Sepharose, 16/10) and eluted with TD buffer against a NaCl gradient of 0 to 500mM in 75 minutes, at a flow rate of 5ml/min. The protein eluted between 0.21 and 0.24M NaCl. The protein-containing fractions were selected from SDS-PAGE analysis, and concentrated to ca 1ml.

The concentrated fractions were loaded at 4 C onto a size exclusion column (Pharmacia S200HR) , and eluted with TD buffer containing NaCl at 500mM. The fractions containing PS were confirmed by SDS-PAGE analysis. The fractions were pooled and dialysed overnight against TD buffer (at least 21) .

The dialysed protein solution was loaded at room temperature onto an affinity column (Pharmacia Blue Sepharose HiLoad 16/10) and eluted with at least five column volumes of TD buffer containing lOmM ATP. This effectively eluted all the protein, although this was not monitored directly.

ATP was removed from the eluant by repeated cycles (at least 5) of concentration (in a stirred cell concentrator (Amicon7 Ultrafiltration Cell) under pressure in an N₂ atmosphere) and dilution with TD buffer; ATP content was monitored by the UV spectrum (220-300nm) of the solution. The protein was finally concentrated (Ultrafree7 concentrator) to a concentration of between 20 and 30 mg/ml . At this concentration, the solution could be aliquoted and frozen directly at -80 C without damage to the protein.

For the purification of the SeMet protein, some precautions were taken to minimise oxidation of the selenium in the protein. The DTT concentration in all buffers was raised to 5mM, all buffers were thoroughly purged with N₂ gas before use, and the whole procedure was completed as fast as possible, within two days. The SeMet preparations of PS were subjected to Electrospray Mass Spectrometry (ESMS) to confirm the incorporation of selenomethionine during the expression.

2. Preparation of Crystals.

Crystals of PS and SeMet PS were grown using the hanging drop vapour diffusion method. Protein (20mg/ml) was mixed on a 1:1 ratio with crystallisation solution containing 4-7% (w/w) Polyethylene Glycol 4000 and 50mM Tris/HCl buffer at pH8. Crystals formed within 2-4 days at 19 C. Crystallisation of SeMet PS, was performed using a nearly identical protocol, but additionally, 2mM DTT was added to the crystallisation solution before mixing the drop.

Crystals ideally have approximate dimensions of 600x200x50 μm. Under non-optimal conditions, crystals grow in clusters and are generally much thinner in the 3^rd dimension (10-20 μm) .

Crystals of PS were cryo-protected using a protocol of gradual soaking in the cryo-protectant, glycerol. A crystal was placed in 20ul of crystallisation solution, and the concentration of glycerol is gradually increased to 28% (v/v) in 4% increments.

3. Structural Determination

Multi-wavelength data sets were collected from a cryo-cooled crystal of SeMet PS, on beam line X-25 of the NSLS at

Brookhaven National Laboratories on Long Island, USA. This is a high-flux station with good intensity and wavelength stability. The presence of selenomethionine in the protein was confirmed independently by electrospray mass spectrometry. Before the experiment, a large number of crystals were extensively screened for highest resolution, low mosaicity and low background scatter.

Terminal radiation-induced diffraction decay was evident in the first crystal to be exposed, which influenced data collection from the second, final SeMet crystal.

In addition to the three data sets collected from SeMet crystals, a data set was collected from a large native crystal, which had been established to be nearly isomorphous with the SeMet crystals used. In order to have complete but also high resolution data, the same oscillation range was exposed twice, the first for measuring low resolution data (i.e. short exposures), and the second for the highest resolution possible (long exposures) . All data were processed using MOSFLM (Leslie, Joint CCP4 and EESF-EACMB Newsletter on Protein Crystallography, Vol.26, Daresbury Laboratory, UK) and scaled with SCALA (Collaborative Computational Project 4. The CCP4 Suite: Programs for Protein Crystallography, Acta Crystallographica, D50, (1994), 760-763).

The selenium atoms were located using the program SnB (Weeks et al., J. of Applied Crystallography, 32, (1999) , 120-124) and their positions refined using SHARP (LaFortelle et al . ,

Methods in Enzymology, 276, (1997), 472-494 and LaFortelle et al . , Maximum Likelihood Refinement in a Graphical environment, with SHARP, in CCP4 study week-end : Recent Advances in Phasing, ed. Wilson et al . , Daresbury Laboratory, UK). The final model contained 19 selenium sites which were used to provide initial phasing. Solvent flattening and phase extension techniques were used to produce an interpretable electron density map.

The program 0 was used for model building. The experimental, solvent flattened electron density map was readily interpretable and secondary structural elements were clearly defined in the electron density bones (calculated with MAPMAN, see Kleywegt et al., Acta Crystallographica, D52, (1996b), 826-828) . The main chain of one monomer could be traced nearly continuously, using the secondary structure template building functionality in 0, and the selenium atoms identified using SHARP providing guidance for chain-tracing. The complete main chain model of monomer A was manually rotated to correspond with the bones of the second monomer (B) . Since the relative orientation of the two domains was slightly different in monomer B, it was optimised by rigid body refinement (using REFMAC, see Murshudov et al., Acta

Crystallographica, D53, (1997) , 24-255) , keeping separate the two domains (residues 1-176 and 177-283) .

The model was improved by three iterated cycles of restrained and individual isotropic maximum likelihood refinement with

REFMAC (40-1.7D resolution) together with manual rebuilding in 0. σ_A-weighted 2F_{0 S}-F_Caic and F₀bs-F_Caic maps were used (Read, Acta Crystallographica, A42, (1986), 140-149), the former frequently informative even when contoured at only 0.8-0.9 map standard deviations. For difficult parts of the model, maps and models resulting from simulated annealing in CNS (Brunger et al., Acta Crystallographica , D54, (1998), 905-921) were also considered. Ordered water molecules were modelled by automated cycles of water addition and removal by ARP (Perrakis et al., Acta Crystallographica, D55, (1999), 1765- 1770) and refinement by REFMAC, with a final cycle of refinement with bulk solvent correction using CNS to ensure good geometry.

The final model consists of 4290 non-hydrogen protein atoms, and 384 water molecules. All residues were modelled, but electron density was poor for C-terminal residues (A283, B282- 3), as well as residues B187-193; the B-factors of these residues are high, approaching 80A². Residues A251-259, B63- 68 and B251-259, though visible, are also not well ordered and have B-factors approaching 60A ². Two residues (A4 and A273) have alternative conformations, and 12 surface-exposed side chains are disordered and were modelled as the most common rotamer at zero occupancy. Table 3 provides model parameters and refinement statistics ^"_ for a version of the model which is essentially the same as that of Table 1 but contains more water molecules and also two ethanediol molecules and a Tris molecule. Residues B188-192 of this version of the model were reconstructed using BUSTER (Bricogne, Methods in Enzymology, 276, (1997), 361-423) in its implementation with TNT (Tronrud, Methods in Enzymology, 277 , (1997), 306-319) instead of by the symmetry operation described above under "PS Structural Characterization". The program DDQ (van den Akker et al . , Acta Crystallographica, D55, (1999), 206-218) was used to assess local and global accuracy and satisfactory completion of refinement, by considering difference density peaks arising from the final 'model. σ_A-weighted difference maps were calculated in REFMAC, excluding water molecules from the model. Quality of the model and its geometry were assessed by OOPS (Kleywegt et al . , OOPS-a-daisy, CCP4/ESF-EACBM Newsletter on Protein Crystallography, 30, (1994), 20-24), PROCHECK (Laskowski et al., J. Applied Crystallography, 26, (1993), 283-291) and WHATCHECK (Hooft et al . , Nature, 381, (1996), 272). No serious deviations from expected values are present, and warnings either correspond to well-defined justifiable features or else poorly-visible features that have high B- factors anyway. There are no Ramachandran outliers, and 92.2% of residues lie in most favoured regions of the plot.

Identification of Likely Active Sites

Having solved the PS crystal structure it is now evident that in terms of their C_α coordinates, the ATP-binding domains of (i) class I amino-acid tRNA synthetases (tRS) (i.e. EtRS from Thermus thermophilus, Nureki et al . , Science, 267, (1995) 1958-1965; QtRS from E. coli, Perona et al . , Biochemistry, 32, (1993) 8758-8771; MtRS from Thermus aquaticus, Mechulam et al., J. of Molecular Biology, 294, (1999), 1287-1297; and YtRS from Bacillus stearothermophilus, Brick et al., J. of Molecular Biology, 208, (1989), 83-98), (ii) phosphopantetheine adenylyltransferase (PPAT) from E. coli

(Izard et al . , EMBO Journal, 18, (1999), 2021-2030) and (iii) CTP:glycerol-3-phosphate cytidylyltransferase (CGT) from B. subtilis (Weber et al . , Structure wi th Folding and Design, 7,

(1999), 1113-1124) are structurally similar to domain N of PS.

More specifically, the particular class of Rossman fold which characterises tRS, CGT and PPAT consists of five β-strands in a central sheet and a cleft between β-strands βl and β4 at the adenosine-binding site (see Fig. 2c) . PS also has these features. In addition, in all four cases strand β5 is followed by catalytically important residues which form the KMSKS motif discussed below) , and for both PS and tRS strand β5 leads directly into the next domain.

Furthermore, two sequence motifs, HIGH and KMSKS (Barker et al., FEBS Letters, 145, (1982), 191-193), are conserved in tRS proteins and also in the wider superfamily. From mutational studies (First et al . , in Biochemistry, 32, (1993), 13644- 13663) these motifs are known to be involved in ATP binding: the HIGH motif binds the adenine portion of ATP (cytidine in CGT) and the KMSKS motif stabilises the β- and γ-phosphate groups. These motifs are also found in PS and correspond respectively to residues 34-37 and 185-189.

The location of the bound ATP adenine in the structure of QtRS corresponds to within 2 to 3D of the positions of the bound nucleotides in YtRS, PPAT and CGT, i.e. in the cleft between strands βl and β4 of the Rossman fold and against the top of helix l (the location of the HIGH motif) . When this domain of QtRS is aligned with domain N of PS the HIGH (actually HDGH in PS) residues line up very well and the QtRS-bound ATP fits nearly perfectly into the same cleft in PS. Despite this excellent match, there is a difference in the positions of the helices ειo7 (in PS) and αl (in QtRS) relative to the Rossman domain. This is the location of the KMSKS motif. However, by changing conservatively the φ/n-angles of residues Vall75, Prol76, Ilel77 and Metl78 which form the PS inter-domain linker main chain, domain C can be rotated sufficiently to align the KMSKS residues with their QtRS counterparts and thus involve them in phosphate binding.

Fig. 4 shows a Connolly surface generated around the proposed PS active sites. The skilled person would immediately recognise that residues shown in the figure would be involved in respective interactions with Mg²⁺, ATP, pantoate and β- alanine .

The Connolly surface opens besides the ATP ribose group and the walls are formed by fully conserved residues, which are largely hydrophobic but include some polar groups . The catalytically essential Mg²⁺ ion is shown at its most likely position where it is bound to OG_Seri88 OH_Tyrι, O^βl _ATP and O^γl _ATP. This is also the proposed Mg²⁺ binding position in PPAT. Slightly more speculatively, the most favourable conformer of pantoate is shown positioned in a cavity where it appears to satisfy the hydrophobic and hydrogen-bonding interactions of the substrate, as well as being suitably positioned for attack on ATP.

Binding positions for β-alanine may also be proposed, but with less certainty than the binding positions of ATP and pantoate. For example, the β-alanine carboxylate may bind in a conserved, positively charged pocket to Argl23, with Met30, Phe62 and Tyr71 providing a hydrophobic patch to accommodate the two β-alanine methylene groups, and Hisl26 being suitably positioned to deprotonate the NH₃ ⁺ group.

A list of the residues which line the binding pockets is provided in Table 4. Some or all of these residues may be used to model PS active sites in the various aspects of the invention discussed above.

Structure-Based Drug Design

Determination of the 3D structure of PS provides important information about the likely active sites of PS, particularly when comparisons are made with similar enzymes. This information may then be used for rational design of PS inhibitors, e.g. by computational techniques which identify possible binding ligands for the active sites, by enabling linked-fragment approaches to drug design, and by enabling the identification and location of bound ligands using X-ray crystallographic analysis. These techniques are discussed in more detail below.

Greer et al . mentioned above describes an iterative approach to ligand design based on repeated sequences of computer modelling, protein-ligand complex formation and X-ray analysis. Thus novel thymidylate synthase inhibitor series were designed de novo by Greer et al., and PS inhibitors may also be designed in the this way. More specifically, using e.g. GRID on the solved 3D structure of PS, a ligand (e.g. a potential inhibitor) for PS may be designed that complements the functionalities of the PS active site(s) . The ligand can then be synthesised, formed into a complex with PS, and the complex then analysed by X-ray crystallography to identify the actual position of the bound ligand. The structure and/or functional groups of the ligand can then be adjusted, if necessary, in view of the results of the X-ray analysis, and the synthesis and analysis sequence repeated until an optimised ligand is obtained. Related approaches to structure-based drug design are also discussed in Bohacek et al . , Medicinal Research Reviews, Vol.16, (1996), 3-50.

As a result of the determination of the PS 3D structure, more purely computational techniques for rational drug design may also be used to design PS inhibitors (for an overview of these techniques see e.g. Walters et al. mentioned above) . For example, automated ligand-receptor docking programs (discussed e.g. by Jones et al . in Current Opinion in Biotechnology, Vol.6, (1995), 652-656) which require accurate information on the atomic coordinates of target receptors may be used to design potential PS inhibitors.

Linked-fragment approaches to drug design also require accurate information on the atomic coordinates of target receptors. The basic idea behind these approaches is to determine (computationally or experimentally) the binding locations of plural ligands to a target molecule, and then construct a molecular scaffold to connect the ligands together in such a way that their relative binding positions are preserved. The ligands may be provided computationally and modelled in a computer system, or provided in an experimental setting, wherein crystals according to the invention are provided and a plurality of ligands soaked separately or in mixed pools into the crystal prior to X-ray analysis and determination of their location.

The binding site of two or more ligands are determined and may be connected to form a potential lead compound that can be further refined using e.g. the iterative technique of Greer et al . For a virtual linked-fragment approach see Verlinde et al . , J. of Computer-Aided Molecular Design, 6, (1992), 131- 147, and for NMR and X-ray approaches see Shuker et al., Science, 274, (1996), 1531-1534 and Stout et al . , Structure, 6, (1998), 839-848. The use of these- approaches to design PS inhibitors is made possible by the determination of the PS structure.

Many of the techniques and approaches to structure-based drug design described above rely at some stage on X-ray analysis to identify the binding position of a ligand in a ligand-protein complex. A common way of doing this is to perform X-ray crystallography on the complex, produce a difference Fourier electron density map, and associate a particular pattern of electron density with the ligand. However, in order to produce the map (as explained e.g. by Blundell et al. mentioned above) it is necessary to know beforehand the protein 3D structure (or at least the protein structure factors) . Therefore, determination of the PS structure also allows difference Fourier electron density maps of PS-ligand complexes to be produced, which can greatly assist the process of rational drug design.

The approaches to structure-based drug design described above all require initial identification of possible compounds for interaction with target bio-molecule (in this case PS) . Sometimes these compounds are known e.g. from the research literature. However, when they are not, or when novel compounds are wanted, a first stage of the drug design program may involve computer-based in silico screening of compound databases (such as the Cambridge Structural Database) with the aim of identifying compounds which interact with the active site or sites of the target bio-molecule. Screening selection criteria may be based on pharmacokinetic properties such as metabolic stability and toxicity. However, determination of the PS structure allows the architecture and chemical nature of each PS active site to be identified, which in turn allows the geometric and functional constraints of a descriptor for the potential modulator of PS activity to be derived. The descriptor is, therefore, a type of virtual 3-D pharmacophore, which can also be used as selection criteria or filter for database screening.

Compounds which have a chemical structure selected using the methods of the invention described herein, wherein said compounds are PS modulators, form a further aspect of the invention. Such compounds may be used in methods of medical treatments, such as in the treatment of bacterial infections in the human or animal body. The compounds may be used alone or in conjunction with other anti-bacterial compounds to enhance their effect.

While the invention has been described in conjunction with the exemplary embodiments described above, many equivalent modifications and variations will be apparent to those skilled in the art when given this disclosure. Accordingly, the exemplary embodiments of the invention set forth are considered to be illustrative and not limiting. Various changes to the described embodiments may be made without departing from the spirit and scope of the invention.

References

Barker et al . , FEBS Letters, 145, (1982), 191-193.

Bohacek et al., Medicinal Research Reviews, Vol.16, (1996), 3- 50.

Brick et al . , J. of Molecular Biology, 208, (1989), 83-98.

Bricogne, Methods in Enzymology, 276, (1997), 361-423.

Brunger et al . , Acta Crystallographica, D54, (1998), 905-921.

Blundell et al . , in Protein Crystallography, Academic Press, New York, London and San Francisco, (1976) .

Blundell et al . , Eur. J. Biochem, Vol. 172, (1988), 513.

Collaborative Computational Project 4. The CCP4 Suite:

Programs for Protein Crystallography, Acta Crystallographica,

D50, (1994), 760-763. Dunbrack et al . , Folding and Design, 2, (1997), 27-42.

First et al., in Biochemistry, 32, (1993), 13644-13663.

Goodford, J. Med. Chem . , 28, (1985), 849-857.

Greer, Science, Vol. 228, (1985), 1055.

Greer et al., J. of Medicinal Chemistry, Vol. 37, (1994), 1035-1054.

Hooft et al., Nature, 381, (1996), 272.

Izard et al., EMBO Journal , 18, (1999), 2021-2030.

Jones et al., Acta Crystallograhy, A47, (1991), 110-119.

Jones et al. in Current Opinion in Biotechnology, Vol.6, (1995), 652-656.

Kleywegt et al . , OOPS-a-daisy, CCP4/ESF-EACBM Newsletter on

Protein Crystallography, 30, (1994), 20-24.

Kleywegt et al . , Acta Crystallographica, D52, (1996b), 826-

828. LaFortelle et al . , Methods in Enzymology, 276, (1997), 472-

494.

LaFortelle et al., Maximum Likelihood Refinement in a

Graphical environment, with SHARP, in CCP4 study week-end:

Recent Advances in Phasing, ed. Wilson et al . , Daresbury Laboratory, UK.

Leslie, Joint CCP4 and EESF-EACMB Newsletter on Protein

Crystallography, Vol.26, Daresbury Laboratory, UK.

Laskowski et al . , J. Applied Crystallography, 26, (1993), 283- 291.

Mechulam et al . , J. of Molecular Biology, 294, (1999), 1287-

1297.

Miyatake et. al, J. Biochem . , 79, (1976), 673-678.

Murshudov et al . , Acta Crystallographica, D53, (1997), 24-255. Nureki et al . , Science, 267, (1995) 1958-1965.

Perona et al . , Biochemistry, 32, (1993) 8758-8771.

Perrakis et al . , Acta Crystallographica, D55, (1999), 1765-

1770.

Read, Acta Crystallographica, A42, (1986), 140-149. Sayle et al . , TIBS, Vol. 20, (1995), 374.

Shuker et al . , Science, 274, (1996), 1531-1534.

Stout et al., Structure, 6, (1998), 839-848.

Tronrud, Methods in Enzymology, 277, (1997), 306-319. van den Akker et al . , Acta Crystallographica, D55, (1999), 206-218. van Duyne et al. , J. Mol . Biol . , 229, (1993), 105-124.

Verlinde et al., J. of Computer-Aided Molecular Design, 6,

(1992), 131-147.

Walters et al . , Drug Discovery Today, Vol.3, No.4, (1998), 160-178.

Weber et al . , Structure wi th Folding and Design, 7, (1999),

1113-1124.

Weeks et al . , J. of Applied Crystallography, 32, (1999) , 120-

124. Table 1

REMARK Written by O version 6.2 .1

REMARK Sun Dec IS ) 17:28: 32 1999

CRYST1 66. 031 78.075 77.126 90.00 103.71 90.00

0RIGX1 1.000000 0. 000000 0.000000 0.00000

ORIGX2 0.000000 1. 000000 0.000000 0.00000

ORIGX3 0.000000 0. ,000000 1.000000 0.00000

SCALE1 0.015144 0. .000000 0.003694 0.00000

SCALE2 0.000000 0. ,012808 0.000000 0.00000

SCALE3 0.000000 0. .000000 0.013346 0.00000

Monomer A

Atom X Y Z Occ. B Atomic type No •

ATOM 1 N MET A 1 21.480 5.652 9.350 1. 00 40. 77 7

ATOM 2 CA MET A 1 22.828 6.214 9.115 1. 00 37. 51 6

ATOM 3 C MET A 1 23.471 6.721 10.394 1. 00 37. 12 6

ATOM 4 O MET A 1 22.954 7.659 10.999 1. 00 37. 52 8

ATOM 5 CB MET A 1 22.777 7.385 8.130 1. 00 35. 78 6

ATOM 6 CG MET A 1 24.222 7.748 7.741 1. 00 33. 60 6

ATOM 7 SD MET A 1 24.158 8.882 6.335 1. 00 30. 36 16

ATOM 8 CE MET A 1 23.874 10.429 7.197 1. 00 27. 91 6

ATOM 9 N LEU A 2 24.565 6.125 10.835 1. 00 33. 76 7

ATOM 10 CA LEU A 2 25.238 6.573 12.014 1. 00 33. 24 6

ATOM 11 C LEU A 2 26.150 7.745 11.696 1. 00 32. 31 6

ATOM 12 O LEU A 2 26.856 7.637 10.679 1. 00 31. 54 8

ATOM 13 CB LEU A 2 26.138 5.467 12.571 1. 00 36. 11 6

ATOM 14 CG LEU A 2 25.578 4.098 12.886 1. 00 40. 23 6

ATOM 15 CD1 LEU A 2 26.741 3.164 13.253 1. 00 39. 01 6

ATOM 16 CD2 LEU A 2 24.566 4.121 14.018 1. ,00 40. ,87 6

ATOM 17 N ILE A 3 26.233 8.778 12.481 1. ,00 30. ,54 7

ATOM 18 CA ILE A 3 27.148 9.869 12.303 1. ,00 30. .81 6

ATOM 19 C ILE A 3 28.090 9.801 13.509 1. .00 31. .50 6

ATOM 20 o ILE A 3 27.616 9.918 14.642 1. ,00 31. ,89 8

ATOM 21 CB ILE A 3 26.523 11.280 12.249 1. ,00 31. ,52 6

ATOM 22 CGI ILE A 3 25.579 11.383 11.041 1. .00 34. .35 6

ATOM 23 CG2 ILE A 3 27.610 12.348 12.227 1. .00 33. .27 6

ATOM 24 GDI ILE A 3 24.913 12.769 11.018 1. .00 34. .98 6

ATOM 25 N ILE A 4 29.350 9.493 13.296 1. .00 26. .66 7

ATOM 26 CA ILE A 4 30.352 9.345 14.340 1. .00 27. .86 6

ATOM 27 c ILE A 4 31.314 10.510 14.337 1. .00 28. .36 6

ATOM 28 O ILE A 4 31.896 10.956 13.322 1. .00 26. .38 8

ATOM 29 CB ILE A 4 31.105 7.998 14.143 1, .00 27, .57 6

ATOM 30 CGI ILE A 4 30.125 6.847 13.972 0, .50 27, .40 6

ATOM 31 CG2 ILE A 4 32.067 7.779 15.312 0 .50 26 .53 6

ATOM 32 GDI ILE A 4 29.201 6.526 15.113 0. .50 28, .00 6

ATOM 33 N GLU A 5 31.633 11.053 15.537 1, .00 25, .12 7

ATOM 34 CA GLU A 5 32.526 12.186 15.655 1 .00 28 .91 6

ATOM 35 c GLU A 5 33.843 11.934 16.357 1 .00 26 .18 6

ATOM 36 O GLU A 5 34.724 12.779 16.300 1 .00 27 .45 8

ATOM 37 CB GLU A 5 31.769 13.303 16.441 1 .00 31 .10 6

ATOM 38 CG GLU A 5 30.611 13.871 15.627 1 .00 34 .62 6

ATOM 39 CD GLU A 5 29.795 14.929 16.355 1 .00 40 .38 6

ATOM 40 OE1 GLU A 5 30.263 15.579 17.306 1 .00 41 .78 8

ATOM 41 OE2 GLU A 5 28.625 15.153 15.971 1 .00 43 .11 8

ATOM 42 N THR A 6 33.976 10.823 17.094 1 .00 27 .41 7

ATOM 43 CA THR A 6 35.188 10.587 17.848 1 .00 27 .21 6

ATOM 44 c THR A 6 35.969 9.345 17.384 1 .00 26 .94 6

ATOM 45 o THR A 6 35.294 8.397 16.960 1 .00 25 .74 8

ATOM 46 CB THR A 6 34.867 10.400 19.351 1 .00 29 .81 6

ATOM 47 OG1 THR A 6 34.175 9.170 19.608 1 .00 30 .13 8

ATOM 48 CG2 THR A 6 33.967 11.528 19.852 1 .00 29 .59 6

ATOM 49 N LEU A 7 37.249 9.359 17.679 1 .00 27 .76 7

ATOM 50 CA LEU A 7 38.052 8.175 17.280 1 .00 27 .99 6

ATOM 51 c LEU A 7 37.684 6.899 18.006 1 .00 29 .61 6

ATOM 52 O LEU A 7 37.546 5.845 17.381 1 .00 26 .94 8

ATOM 53 CB LEU A 7 39.526 8.515 17.460 1 . 00 28 .02 6

ATOM 54 CG LEU A 7 40.011 9.725 16.678 1 .00 31 .71 6 ATOM 55 CD1 LEU A 7 41.523 9.840 16.799 1.00 34.04 6

ATOM 56 CD2 LEU A 7 39.612 9.641 15.219 1.00 32.76 6

ATOM 57 N PRO A 8 37.434 6.913 19.313 1.00 30.58 7

ATOM 58 CA PRO A 8 37.081 5.687 20.013 1.00 29.86 6

ATOM 59 c PRO A 8 35.814 5.062 19.505 1.00 28.23 6

ATOM 60 O PRO A 8 35.701 3.845 19.394 1.00 25.90 8

ATOM 61 CB PRO A 8 37.001 6.107 21.485 1.00 31.83 6

ATOM 62 CG PRO A 8 37.816 7.345 21.593 1.00 31.44 6

ATOM 63 CD PRO A 8 37.601 8.053 20.243 1.00 30.62 6

ATOM 64 N LEU A 9 34.754 5.838 19.239 1.00 27.49 7

ATOM 65 CA LEU A 9 33.489 5.349 18.746 1.00 28.03 6

ATOM 66 c LEU A 9 33.625 4.896 17.281 1.00 25.69 6

ATOM 67 O LEU A 9 32.960 3.907 16.978 1.00 26.00 8

ATOM 68 CB LEU A 9 32.376 6.393 18.920 1.00 31.67 6

ATOM 69 CG LEU A 9 32.089 6.741 20.400 1.00 35.64 6

ATOM 70 CD1 LEU A 9 31.037 7.824 20.573 1.00 35.73 6

ATOM 71 CD2 LEU A 9 31.636 5.493 21.154 1.00 37.26 6

ATOM 72 N LEU A 10 34.532 5.512 16.526 1.00 25.45 7

ATOM 73 CA LEU A 10 34.763 5.045 15.154 1.00 23.19 6

ATOM 74 c LEU A 10 35.461 3.678 15.228 1.00 23.87 6

ATOM 75 O LEU A 10 35.017 2.730 14.592 1.00 23.85 8

ATOM 76 CB LEU A 10 35.577 6.082 14.350 1.00 21.87 6

ATOM 77 CG LEU A 10 36.012 5.560 12.953 1.00 22.51 6

ATOM 78 GDI LEU A 10 34.829 5.397 12.007 1.00 22.75 6

ATOM 79 CD2 LEU A 10 37.072 6.488 12.337 1.00 23.02 6

ATOM 80 N ARG A 11 36.423 3.571 16.150 1.00 25.14 7

ATOM 81 CA ARG A 11 37.191 2.304 16.232 1.00 28.37 6

ATOM 82 c ARG A 11 36.236 1.209 16.642 1.00 29.20 6

ATOM 83 O ARG A 11 36.288 0.113 16.066 1.00 27.74 8

ATOM 84 CB ARG A 11 38.399 2.556 17.142 1.00 31.48 6

ATOM 85 CG ARG A 11 39.141 1.279 17.544 1.00 36.42 6

ATOM 86 CD ARG A 11 40.384 1.586 18.401 1.00 40.76 6

ATOM 87 NE ARG A 11 40.948 0.327 18.857 1.00 44.29 7 TOM 88 cz ARG A 11 40.627 -0.524 19.819 1.00 45.48 6

ATOM 89 NH1 ARG A 11 39.610 -0.297 20.644 1.00 47.34 7

ATOM 90 NH2 ARG A 11 41.306 -1.656 20.008 1.00 45.04 7

ATOM 91 N GLN A 12 35.347 1.474 17.591 1.00 26.32 7

ATOM 92 CA GLN A 12 34.364 0.453 17.968 1.00 28.52 6

ATOM 93 c GLN A 12 33.550 -0.050 16.798 1.00 27.48 6

ATOM 94 O GLN A 12 33.340 -1.248 16.579 1.00 25.61 8

ATOM 95 CB GLN A 12 33.450 1.032 19.051 1.00 30.81 6

ATOM 96 CG GLN A 12 32.364 0.022 19.483 1.00 34.43 6

ATOM 97 CD GLN A 12 31.513 0.662 20.570 1.00 37.80 6

ATOM 98 OE1 GLN A 12 31.804 0.354 21.743 1.00 43.75 8

ATOM 99 NE2 GLN A 12 30.545 1.495 20.293 1.00 38.11 7

ATOM 100 N GLN A 13 32.938 0.879 16.025 1.00 25.56 7

ATOM 101 CA GLN A 13 32.110 0.497 14.901 1.00 24.82 6

ATOM 102 c GLN A 13 32.889 -0.235 13.804 1.00 23.46 6

ATOM 103 o GLN A 13 32.360 -1.209 13.326 1.00 24.23 8

ATOM 104 CB GLN A 13 31.427 1.706 14.213 1.00 28.90 6

ATOM 105 CG GLN A 13 30.471 2.397 15.154 1.00 34.73 6

ATOM 106 CD GLN A 13 29.201 1.611 15.405 1.00 37.69 6

ATOM 107 OE1 GLN A 13 28.697 0.913 14.519 1.00 40.12 8

ATOM 108 NE2 GLN A 13 28.765 1.760 16.646 1.00 39.64 7

ATOM 109 N ILE A 14 34.075 0.258 13.493 1.00 21.48 7

ATOM 110 CA ILE A 14 34.904 -0.413 12.482 1.00 23.36 6

ATOM 111 c ILE A 14 35.252 -1.833 12.978 1.00 23.78 6

ATOM 112 o ILE A 14 35.100 -2.754 12.163 1.00 24.98 8

ATOM 113 CB ILE A 14 36.157 0.388 12.154 1.00 24.05 6

ATOM 114 CGI ILE A 14 35.752 1.756 11.492 1.00 23.68 6

ATOM 115 CG2 ILE A 14 37.152 -0.372 11.258 1.00 23.44 6

ATOM 116 GDI ILE A 14 34.981 1.571 10.185 1.00 22.33 6

ATOM 117 N ARG A 15 35.691 -1.946 14.210 1.00 24.68 7

ATOM 118 CA ARG A 15 36.062 -3.331 14.658 1.00 24.36 6

ATOM 119 C ARG A 15 34.868 -4.230 14.500 1.00 24.62 6

ATOM 120 O ARG A 15 34.925 -5.358 13.991 1.00 26.61 8

ATOM 121 CB ARG A 15 36.618 -3.304 16.087 1.00 24.77 6

ATOM 122 CG ARG A 15 38.037 -2.760 16.169 1.00 29.78 6

ATOM 123 CD ARG A 15 38.488 -2.556 17.609 1.00 31.54 6

ATOM 124 NE ARG A 15 38.632 -3.872 18.241 1.00 34.58 7

ATOM 125 CZ ARG A 15 39.603 -4.741 17.996 1.00 36.36 6

ATOM 126 NH1 ARG A 15 40.588 -4.484 17.142 1.00 37.87 7

ATOM 127 NH2 ARG A 15 39.609 -5.896 18.638 1.00 37.41 7

ATOM 128 N ARG A 16 33.681 -3.788 14.925 1.00 23.16 7 ATOM 129 CA ARG A 16 32.495 -4.643 14.843 1.00 24.97 6

ATOM 130 C ARG A 16 32.091 -5.007 13.453 1.00 26.58 6

ATOM 131 O ARG A 16 31.688 -6.112 13.134 1.00 25.54 8

ATOM 132 CB ARG A 16 31.335 -3.905 15.565 1.00 26.81 6

ATOM 133 CG ARG A 16 31.739 -3.858 17.037 1.00 30.82 6

ATOM 134 CD ARG A 16 30.609 -3.393 17.953 1.00 35.27 6

ATOM 135 NE ARG A 16 31.145 -3.440 19.331 1.00 38.72 7

ATOM 136 CZ ARG A 16 30.380 -3.407 20.431 1.00 41.50 6

ATOM 137 NH1 ARG A 16 29.057 -3.350 20.279 1.00 41.64 7

ATOM 138 NH2 ARG A 16 30.986 -3.478 21.616 1.00 40.81 7

ATOM 139 N LEU A 17 32.236 -4.016 12.503 1.00 25.60 7

ATOM 140 CA LEU A 17 31.869 -4.342 11.148 1.00 25.51 6

ATOM 141 C LEU A 17 32.796 -5.382 10.547 1.00 25.77 6

ATOM 142 O LEU A 17 32.287 -6.296 9.882 1.00 27.72 8

ATOM 143 CB LEU A 17 31.929 -3.067 10.251 1.00 26.53 6

ATOM 144 CG LEU A 17 30.763 -2.131 10.574 1.00 28.03 6

ATOM 145 CD1 LEU A 17 31.127 -0.707 10.125 1.00 29.84 6

ATOM 146 CD2 LEU A 17 29.455 -2.554 9.941 1.00 30.48 6

ATOM 147 N ARG A 18 34.062 -5.187 10.811 1.00 25.72 7

ATOM 148 CA ARG A 18 35.021 -6.172 10.278 1.00 26.50 6

ATOM 149 C ARG A 18 34.894 -7.544 10.989 1.00 27.79 6

ATOM 150 O ARG A 18 34.993 -8.564 10.329 1.00 26.32 8

ATOM 151 CB ARG A 18 36.436 -5.665 10.405 1.00 28.86 6

ATOM 152 CG ARG A 18 36.506 -4.291 9.685 1.00 31.17 6

ATOM 153 CD ARG A 18 37.972 -4.010 9.471 1.00 36.04 6

ATOM 154 NE ARG A 18 38.502 -4.834 8.364 1.00 39.73 7

ATOM 155 CZ ARG A 18 39.788 -5.197 8.409 1.00 41.34 6

ATOM 156 NHl ARG A 18 40.523 -4.806 9.456 1.00 42.67 7

ATOM 157 NH2 ARG A 18 40.324 -5.921 7.432 1.00 41.84 7

ATOM 158 N MET A 19 34.537 -7.458 12.259 1.00 25.78 7 TOM 159 CA MET A 19 34.344 -8.735 13.010 1.00 27.53 6

ATOM 160 C MET A 19 33.230 -9.524 12.371 1.00 26.64 6

ATOM 161 O MET A 19 33.236 -10.747 12.181 1.00 25.81 8

ATOM 162 CB MET A 19 34.097 -8.377 14.473 1.00 24.76 6

ATOM 163 CG MET A 19 33.680 -9.547 15.350 1.00 26.07 6

ATOM 164 SD MET A 19 31.960 -10.075 15.286 1.00 24.59 16

ATOM 165 CE MET A 19 31.123 -8.581 15.796 1.00 28.15 6

ATOM 166 N GLU A 20 32.202 -8.844 11.855 1.00 28.38 7

ATOM 167 CA GLU A 20 31.083 -9.471 11.156 1.00 28.35 6

ATOM 168 C GLU A 20 31.345 -9.875 9.720 1.00 31.76 6

ATOM 169 O GLU A 20 30.395 -10.362 9.077 1.00 32.53 8

ATOM 170 CB GLU A 20 29.874 -8.502 11.103 1.00 30.90 6

ATOM 171 CG GLU A 20 29.474 -8.103 12.493 1.00 31.14 6

ATOM 172 N GLY A 21 32.531 -9.676 9.217 1.00 29.46 7

ATOM 173 CA GLY A 21 32.968 -10.045 7.901 1.00 30.44 6

ATOM 174 C , GLY A 21 32.503 -9.016 6.844 1.00 28.10 6

ATOM 175 0 GLY A 21 32.465 -9.457 5.705 1.00 30.38 8

ATOM 176 N LYΞ A 22 32.195 -7.815 7.269 1.00 27.01 7

ATOM 177 CA LYS A 22 31.684 -6.909 6.184 1.00 26.80 6

ATOM 178 C LYS A 22 32.855 -6.293 5.441 1.00 26.41 6

ATOM 179 o LYS A 22 33.844 -5.944 6.097 1.00 27.41 8

ATOM 180 CB LYS A 22 30.773 -5.883 6.825 1.00 27.50 6

ATOM 181 CG LYS A 22 29.392 -6.529 7.152 1.00 32.21 6

ATOM 182 CD LYS A 22 28.721 -5.570 8.118 1.00 37.87 6

ATOM 183 CE LYS A 22 27.207 -5.752 8.159 1.00 42.38 6 TOM 184 NZ LYS A 22 26.574 -4.400 8.447 1.00 46.00 7

ATOM 185 N ARG A 23 32.737 -6.159 4.128 1.00 26.60 7

ATOM 186 CA ARG A 23 33.781 -5.503 3.325 1.00 27.62 6

ATOM 187 C ARG A 23 33.468 -4.008 3.350 1.00 25.54 6

ATOM 188 O ARG A 23 32.293 -3.677 3.209 1.00 25.62 8

ATOM 189 CB ARG A 23 33.784 -6.101 1.934 1.00 31.46 6

ATOM 190 CG ARG A 23 34.506 -5.433 0.801 1.00 39.27 6 TOM 191 CD ARG A 23 34.206 -5.965 -0.610 1.00 43.15 6

ATOM 192 NE ARG A 23 35.366 -5.731 -1.466 1.00 45.63 7

ATOM 193 CZ ARG A 23 36.577 -6.268 -1.262 1.00 46.18 6

ATOM 194 NHl ARG A 23 36.841 -7.101 -0.272 1.00 47.31 7 TOM 195 NH2 ARG A 23 37.537 -5.954 -2.117 1.00 48.28 7

ATOM 196 N VAL A 24 34.412 -3.165 3.697 1.00 23.62 7

ATOM 197 CA VAL A 24 34.196 -1.743 3.900 1.00 22.06 6

ATOM 198 C VAL A 24 34.785 -0.891 2.782 1.00 17.49 6

ATOM 199 o VAL A 24 35.924 -1.166 2.392 1.00 18.13 8

ATOM 200 CB VAL A 24 34.830 -1.279 5.218 1.00 22.91 6

ATOM 201 CGI . VAL A 24 34.677 0.198 5.452 1.00 24.86 6

ATOM 202 CG2 : VAL A 24 34.173 -2.010 6.405 1.00 24.10 6 ATOM 203 N ALA A 25 34.023 0.099 2.315 1.00 17.82 7

ATOM 204 CA ALA A 25 34.597 0.939 1.279 1.00 18.16 6

ATOM 205 C ALA A 25 34.593 2.272 2.004 1.00 18.48 6

ATOM 206 O ALA A 25 33.673 2.667 2.768 1.00 22.08 8

ATOM 207 CB ALA A 25 33.863 1.032 -0.030 1.00 20.30 6

ATOM 208 N LEU A 26 35.579 3.142 1.726 1.00 16.71 7

ATOM 209 CA LEU A 26 35.791 4.438 2.266 1.00 16.65 6

ATOM 210 C LEU A 26 35.819 5.507 1.152 1.00 17.57 6

ATOM 211 O LEU A 26 36.497 5.321 0.146 1.00 18.90 8

ATOM 212 CB LEU A 26 37.120 4.628 3.038 1.00 18.22 6

ATOM 213 CG LEU A 26 37.458 6.066 3.461 1.00 18.69 6

ATOM 214 CD1 LEU A 26 36.500 6.657 4.511 1.00 20.43 6

ATOM 215 CD2 LEU A 26 38.887 6.061 4.006 1.00 20.45 6

ATOM 216 N VAL A 27 35.065 6.569 1.318 1.00 16.54 7

ATOM 217 CA VAL A 27 35.028 7.712 0.418 1.00 16.69 6

ATOM 218 C VAL A 27 35.493 8.915 1.208 1.00 15.96 6

ATOM 219 O VAL A 27 34.643 9.495 1.891 1.00 17.62 8

ATOM 220 CB VAL A 27 33.636 8.038 -0.196 1.00 18.00 6

ATOM 221 CGI VAL A 27 33.738 9.238 -1.157 1.00 21.63 6

ATOM 222 CG2 VAL A 27 33.057 6.801 -0.869 1.00 20.05 6

ATOM 223 N PRO A 28 36.728 9.403 1.100 1.00 18.63 7

ATOM 224 CA PRO A 28 37.265 10.543 1.776 1.00 19.42 6

ATOM 225 C PRO A 28 36.814 11.864 1.198 1.00 20.36 6

ATOM 226 O PRO A 28 36.941 11.994 -0.024 1.00 21.38 8

ATOM 227 CB PRO A 28 38.775 10.466 1.589 1.00 23.04 6

ATOM 228 CG PRO A 28 39.036 9.147 0.945 1.00 23.71 6

ATOM 229 CD PRO A 28 37.765 8.641 0.309 1.00 19.69 6

ATOM 230 N THR A 29 36.209 12.765 1.957 1.00 20.05 7

ATOM 231 CA THR A 29 35.752 14.046 1.426 1.00 20.41 6

ATOM 232 C THR A 29 36.036 15.159 2.439 1.00 18.55 6

ATOM 233 O THR A 29 36.271 14.922 3.618 1.00 19.34 8

ATOM 234 CB THR A 29 34.254 14.069 1.053 1.00 21.16 6

ATOM 235 OG1 THR A 29 33.512 14.439 2.242 1.00 19.82 8

ATOM 236 CG2 THR A 29 33.658 12.762 0.537 1.00 20.33 6

ATOM 237 N MET A 30 35.897 16.391 2.003 1.00 20.47 7

ATOM 238 CA MET A 30 35.998 17.616 2.811 1.00 20.82 6

ATOM 239 C MET A 30 34.587 18.281 2.815 1.00 23.33 6

ATOM 240 0 MET A 30 34.465 19.488 3.115 1.00 23.42 8

ATOM 241 CB MET A 30 37.065 18.623 2.375 1.00 21.06 6

ATOM 242 CG MET A 30 38.446 17.925 2.357 1.00 21.02 6

ATOM 243 SD MET A 30 39.740 19.108 2.816 1.00 24.24 16

ATOM 244 CE MET A 30 39.431 20.461 1.687 1.00 26.95 6

ATOM 245 N GLY A 31 33.576 17.477 2.616 1.00 21.21 7

ATOM 246 CA GLY A 31 32.189 17.985 2.705 1.00 24.38 6

ATOM 247 C GLY A 31 31.835 18.946 1.563 1.00 24.71 6

ATOM 248 O GLY A 31 32.498 18.909 0.524 1.00 22.94 8

ATOM 249 N ASN A 32 30.712 19.650 1.637 1.00 24.08 7

ATOM 250 CA ASN A 32 30.269 20.550 0.552 1.00 22.88 6

ATOM 251 C ASN A 32 29.995 19.636 -0.655 1.00 22.70 6

ATOM 252 O ASN A 32 30.519 19.801 -1.762 1.00 25.35 8

ATOM 253 CB ASN A 32 31.269 21.654 0.253 1.00 27.38 6

ATOM 254 CG ASN A 32 30.612 22.708 -0.658 1.00 31.01 6

ATOM 255 OD1 ASN A 32 29.390 22.842 -0.531 1.00 33.26 8

ATOM 256 ND2 ASN A 32 31.392 23.283 -1.538 1.00 31.51 7

ATOM 257 N LEU A 33 29.250 18.551 -0.428 1.00 22.17 7

ATOM 258 CA LEU A 33 29.111 17.438 -1.343 1.00 20.92 6

ATOM 259 C LEU A 33 28.300 17.796 -2.594 1.00 23.49 6

ATOM 260 O LEU A 33 27.325 18.519 -2.397 1.00 25.06 8

ATOM 261 CB LEU A 33 28.479 16.200 -0.668 1.00 21.06 6

ATOM 262 CG LEU A 33 29.372 15.713 0.501 1.00 21.76 6

ATOM 263 CD1 LEU A 33 28.821 14.431 1.108 1.00 24.92 6

ATOM 264 CD2 LEU A 33 30.834 15.495 0.073 1.00 21.13 6

ATOM 265 N HIS A 34 28.691 17.217 -3.706 1.00 21.31 7

ATOM 266 CA HIS A 34 27.929 17.454 -4.953 1.00 19.68 6

ATOM 267 C HIS A 34 27.793 16.165 -5.698 1.00 21.69 6

ATOM 268 O HIS A 34 28.073 15.035 -5.218 1.00 21.01 8

ATOM 269 CB HIS A 34 28.648 18.575 -5.722 1.00 20.00 6

ATOM 270 CG HIS A 34 30.062 18.267 -6.078 1.00 23.69 6

ATOM 271 ND1 HIS A 34 30.449 17.170 -6.770 1.00 26.07 7

ATOM 272 CD2 HIS A 34 31.211 18.953 -5.778 1.00 26.19 6

ATOM 273 CE1 HIS A 34 31.776 17.161 -6.890 1.00 27.03 6

ATOM 274 NE2 HIS A 34 32.262 18.221 -6.296 1.00 27.65 7

ATOM 275 N ASP A 35 27.277 16.218 -6.957 1.00 20.96 7

ATOM 276 CA ASP A 35 26.992 15.008 -7.685 1.00 21.21 6 ATOM 277 C ASP A 35 28.213 14.132 -7.962 1.00 20.16 6

ATOM 278 O ASP A 35 28.006 12.921 -8.079 1.00 22.17 8

ATOM 279 CB ASP A 35 26.386 15.393 -9.061 1.00 23.09 6

ATOM 280 CG ASP A 35 24.959 15.842 -8.957 1.00 26.28 6

ATOM 281 OD1 ASP A 35 24.273 15.662 -7.929 1.00 27.10 8

ATOM 282 OD2 ASP A 35 24.439 16.326 ^• -10.018 1.00 25.60 8

ATOM 283 N GLY A 36 29.375 14.766 -8.056 1.00 21.98 7

ATOM 284 CA GLY A 36 30.620 14.030 -8.244 1.00 21.77 6

ATOM 285 C GLY A 36 30.786 13.041 -7.065 1.00 22.77 6

ATOM 286 O GLY A 36 31.157 11.870 -7.245 1.00 22.33 8

ATOM 287 N HIS A 37 30.620 13.573 -5.849 1.00 22.48 7

ATOM 288 CA HIS A 37 30.753 12.759 -4.642 1.00 19.90 6

ATOM 289 C HIS A 37 29.688 11.715 -4.564 1.00 20.48 6

ATOM 290 O HIS A 37 29.886 10.568 -4.111 1.00 20.51 8

ATOM 291 CB HIS A 37 30.659 13.645 -3.371 1.00 20.77 6

ATOM 292 CG HIS A 37 31.604 14.773 -3.310 1.00 23.28 6

ATOM 293 ND1 HIS A 37 32.947 14.667 -2.929 1.00 28.53 7

ATOM 294 CD2 HIS A 37 31.407 16.089 -3.544 1.00 19.82 6

ATOM 295 CE1 HIS A 37 33.536 15.843 -2.870 1.00 23.53 6

ATOM 296 NE2 HIS A 37 32.585 16.736 -3.250 1.00 26.84 7

ATOM 297 N MET A 38 28.469 11.976 -5.080 1.00 19.18 7

ATOM 298 CA MET A 38 27.409 10.961 -5.035 1.00 19.76 6

ATOM 299 C MET A 38 27.795 9.798 -5.955 1.00 22.39 6

ATOM 300 O MET A 38 27.476 8.670 -5.614 1.00 21.94 8

ATOM 301 CB MET A 38 26.038 11.520 -5.422 1.00 23.14 6

ATOM 302 CG MET A 38 25.482 12.594 -4.447 1.00 25.87 6

ATOM 303 SD MET A 38 25.332 11.996 -2.726 1.00 28.93 16

ATOM 304 CE MET A 38 26.690 12.846 -1.980 1.00 25.74 6

ATOM 305 N LYS A 39 28.493 10.034 -7.069 1.00 19.54 7

ATOM 306 CA LYS A 39 28.943 8.945 -7.921 1.00 21.23 6

ATOM 307 C LYS A 39 29.995 8.090 -7.205 1.00 19.48 6

ATOM 308 O LYS A 39 29.947 6.878 -7.283 1.00 19.63 8

ATOM 309 CB LYS A 39 29.524 9.474 -9.236 1.00 23.04 6

ATOM 310 CG LYS A 39 29.977 8.354 -10.200 1.00 23.73 6

ATOM 311 CD LYS A 39 28.831 7.464 -10.663 1.00 29.69 6

ATOM 312 CE LYS A 39 29.392 6.340 -11.576 1.00 32.23 6

ATOM 313 NZ LYS A 39 28.207 5.549 -12.095 1.00 35.95 7

ATOM 314 N LEU A 40 30.869 8.716 -6.387 1.00 18.59 7

ATOM 315 CA LEU A 40 31.829 7.935 -5.587 1.00 19.30 6

ATOM 316 C LEU A 40 31.065 7.001 -4.652 1.00 17.32 6

ATOM 317 O LEU A 40 31.433 5.818 -4.467 1.00 19.58 8

ATOM 318 CB LEU A 40 32.725 8.865 -4.822 1.00 20.84 6

ATOM 319 CG LEU A 40 33.577 9.868 -5.641 1.00 21.98 6

ATOM 320 CD1 LEU A 40 34.510 10.649 -4.714 1.00 19.78 6

ATOM 321 CD2 LEU A 40 34.368 9.211 -6.759 1.00 22.47 6

ATOM 322 N VAL A 41 30.079 7.532 -3.957 1.00 19.06 7

ATOM 323 CA VAL A 41 29.260 6.732 -3.016 1.00 18.09 6

ATOM 324 C VAL A 41 28.598 5.614 -3.736 1.00 17.62 6

ATOM 325 O VAL A 41 28.537 4.470 -3.258 1.00 19.88 8

ATOM 326 CB VAL A 41 28.253 7.674 -2.265 1.00 20.51 6

ATOM 327 CGI VAL A 41 27.211 6.841 -1.514 1.00 21.02 6

ATOM 328 CG2 VAL A 41 29.010 8.629 -1.336 1.00 19.99 6

ATOM 329 N ASP A 42 28.010 5.882 -4.952 1.00 18.32 7

ATOM 330 CA ASP A 42 27.355 4.768 -5.614 1.00 20.18 6

ATOM 331 C ASP A 42 28.312 3.653 -5.995 1.00 20.77 6

ATOM 332 O ASP A 42 27.977 2.483 -5.943 1.00 22.32 8

ATOM 333 CB ASP A 42 26.667 5.238 -6.920 1.00 22.54 6

ATOM 334 CG ASP A 42 25.531 6.164 -6.652 1.00 24.06 6

ATOM 335 OD1 ASP A 42 24.908 6.188 -5.570 1.00 27.49 8

ATOM 336 OD2 ASP A 42 25.140 6.976 -7.558 1.00 30.83 8

ATOM 337 N GLU A 43 29.539 4.041 -6.419 1.00 20.92 7

ATOM 338 CA GLU A 43 30.528 3.015 -6.753 1.00 22.39 6

ATOM 339 C GLU A 43 30.924 2.224 -5.512 1.00 21.74 6

ATOM 340 O GLU A 43 31.185 1.036 -5.623 1.00 23.66 8

ATOM 341 CB GLU A 43 31.816 3.583 -7.342 1.00 23.36 6

ATOM 342 CG GLU A 43 31.560 4.030 -8.792 1.00 32.68 6

ATOM 343 CD GLU A 43 31.450 2.806 -9.705 1.00 34.94 6

ATOM 344 OE1 , GLU A 43 32.113 1.776 -9.517 1.00 39.24 8

ATOM 345 OE2 : GLU A 43 30.590 2.908 -10.606 1.00 42.50 8

ATOM 346 N ALA A 44 31.103 2.914 -4.372 1.00 21.59 7

ATOM 347 CA ALA A 44 31.413 2.228 -3.131 1.00 20.24 6

ATOM 348 C ALA A 44 30.241 1.299 -2.736 1.00 22.05 6

ATOM 349 O ALA A 44 30.575 0.162 -2.324 1.00 23.77 8

ATOM 350 CB ALA A 44 31.698 3.226 -2.025 1.00 19.63 6 ATOM 351 N LYS A 45 29.033 1.800 -2.843 1.00 24.11 7

ATOM 352 CA LYS A 45 27.888 0.912 -2.499 1.00 26.00 6

ATOM 353 C LYS A 45 27.912 -0.215 -3.471 1.00 27.19 6

ATOM 354 O LYS A 45 27.573 -1.297 -2.970 1.00 28.01 8

ATOM 355 CB LYS A 45 26.550 1.612 -2.555 1.00 28.17 6

ATOM 356 CG LYS A 45 26.331 2.723 -1.544 1.00 33.53 6

ATOM 357 CD LYS A 45 25.613 2.271 -0.277 1.00 40.20 6

ATOM 358 CE LYS A 45 24.365 1.437 -0.586 1.00 42.16 6

ATOM 359 NZ LYS A 45 23.332 1.467 0.475 1.00 47.05 7

ATOM 360 N ALA A 46 28.221 -0.250 -4.714 1.00 25.90 7

ATOM 361 CA ALA A 46 28.227 -1.457 -5.529 1.00 26.79 6

ATOM 362 C ALA A 46 29.360 -2.424 -5.183 1.00 29.75 6

ATOM 363 O ALA A 46 29.233 -3.661 -5.395 1.00 28.75 8

ATOM 364 CB ALA A 46 28.360 -1.038 -6.984 1.00 28.50 6

ATOM 365 N ARG A 47 30.492 -1.922 -4.680 1.00 26.27 7

ATOM 366 CA ARG A 47 31.649 -2.782 -4.511 1.00 25.06 6

ATOM 367 C ARG A 47 31.816 -3.283 -3.103 1.00 25.85 6

ATOM 368 O ARG A 47 32.669 -4.158 -2.954 1.00 29.00 8

ATOM 369 CB ARG A 47 32.921 -1.993 -4.921 1.00 26.64 6

ATOM 370 CG ARG A 47 32.973 -1.664 -6.407 1.00 30.45 6

ATOM 371 CD ARG A 47 34.079 -0.626 -6.688 1.00 30.96 6

ATOM 372 NE ARG A 47 33.831 -0.063 -8.068 1.00 36.09 7

ATOM 373 CZ ARG A 47 34.612 -0.526 -9.051 1.00 37.23 6

ATOM 374 NHl ARG A 47 35.552 -1.422 -8.779 1.00 37.53 7

ATOM 375 NH2 ARG A 47 34.458 -0.076 -10.277 1.00 38.83 7

ATOM 376 N ALA A 48 31.118 -2.729 -2.117 1.00 23.59 7

ATOM 377 CA ALA A 48 31.382 -3.211 -0.762 1.00 23.32 6

ATOM 378 C ALA A 48 30.099 -3.421 0.008 1.00 23.85 6

ATOM 379 O ALA A 48 29.048 -2.891 -0.355 1.00 26.50 8

ATOM 380 CB ALA A 48 32.316 -2.196 -0.069 1.00 24.37 6

ATOM 381 N ASP A 49 30.163 -4.115 1.146 1.00 22.20 7

ATOM 382 CA ASP A 49 28.925 -4.271 1.916 1.00 26.00 6

ATOM 383 C ASP A 49 28.562 -3.133 2.803 1.00 26.80 6

ATOM 384 O ASP A 49 27.400 -2.841 3.120 1.00 28.51 8

ATOM 385 CB ASP A 49 29.066 -5.563 2.775 1.00 31.27 6

ATOM 386 CG ASP A 49 29.809 -6.700 2.149 1.00 35.17 6

ATOM 387 OD1 ASP A 49 30.741 -7.285 2.759 1.00 35.30 8

ATOM 388 OD2 ASP A 49 29.459 -7.142 1.032 1.00 39.32 8

ATOM 389 N VAL A 50 29.551 -2.305 3.185 1.00 21.71 7

ATOM 390 CA VAL A 50 29.379 -1.186 4.072 1.00 24.23 6

ATOM 391 C VAL A 50 30.120 0.032 3.514 1.00 22.66 6

ATOM 392 O VAL A 50 31.259 -0.150 3.088 1.00 23.46 8

ATOM 393 CB VAL A 50 29.980 -1.492 5.460 1.00 28.04 6

ATOM 394 CGI VAL A 50 29.862 -0.274 6.353 1.00 30.12 6

ATOM 395 CG2 VAL A 50 29.310 -2.723 6.087 1.00 31.57 6

ATOM 396 N VAL A 51 29.462 1.181 3.484 1.00 20.55 7

ATOM 397 CA VAL A 51 30.124 2.367 2.940 1.00 18.63 6

ATOM 398 C VAL A 51 30.317 3.377 4.038 1.00 19.83 6

ATOM 399 O VAL A 51 29.382 3.743 4.754 1.00 19.84 8

ATOM 400 CB VAL A 51 29.292 3.029 1.830 1.00 21.12 6

ATOM 401 CGI VAL A 51 29.993 4.288 1.310 1.00 22.56 6

ATOM 402 CG2 VAL A 51 29.015 2.098 0.666 1.00 23.68 6

ATOM 403 N VAL A 52 31.527 3.878 4.198 1.00 18.34 7

ATOM 404 CA VAL A 52 31.884 4.890 5.151 1.00 18.76 6

ATOM 405 C VAL A 52 32.298 6.183 4.450 1.00 20.80 6

ATOM 406 O VAL A 52 33.147 6.104 3.559 1.00 21.14 8

ATOM 407 CB VAL A 52 33.088 4.473 6.034 1.00 20.37 6

ATOM 408 CGI VAL A 52 33.539 5.585 6.978 1.00 19.87 6

ATOM 409 CG2 VAL A 52 32.719 3.217 6.820 1.00 21.14 6

ATOM 410 N VAL A 53 31.712 7.325 4.777 1.00 18.75 7

ATOM 411 CA VAL A 53 32.134 8.568 4.131 1.00 18.32 6

ATOM 412 C VAL A 53 32.759 9.411 5.215 1.00 18.55 6

ATOM 413 O VAL A 53 32.055 9.630 6.225 1.00 19.86 8

ATOM 414 CB VAL A 53 30.949 9.327 3.473 1.00 18.40 6

ATOM 415 CGI VAL A 53 31.462 10.680 2.967 1.00 20.65 6

ATOM 416 CG2 VAL A 53 30.322 8.469 2.396 1.00 17.69 6

ATOM 417 N SER A 54 33.913 9.963 4.996 1.00 16.45 7

ATOM 418 CA SER A 54 34.482 10.911 5.946 1.00 20.30 6

ATOM 419 C SER A 54 34.280 12.349 5.478 1.00 21.22 6

ATOM 420 O SER A 54 34.281 12.545 4.254 1.00 18.83 8

ATOM 421 CB SER A 54 35.971 10.631 6.156 1.00 21.31 6

ATOM 422 OG SER A 54 36.695 10.788 4.949 1.00 21.56 8

ATOM 423 N ILE A 55 33.909 13.223 6.394 1.00 21.28 7

ATOM 424 CA ILE A 55 33.699 14.621 6.108 1.00 19.86 6 ATOM 425 C ILE A 55 34.649 15.356 7.100 1.00 20.76 6

ATOM 426 O ILE A 55 34.344 15.342 8.300 1.00 22. 84 8

ATOM 427 CB ILE A 55 32.273 15.102 6.291 1.00 21. 61 6

ATOM 428 CGI ILE A 55 31.333 14.422 5.255 1.00 21. 20 6

ATOM 429 CG2 ILE A 55 32.222 16.614 6.139 1.00 22. 98 6

ATOM 430 CDl ILE A 55 29.854 14.691 5.584 1.00 24. 15 6

ATOM 431 N PHE A 56 35.723 15.883 6.577 1.00 17. 70 7

ATOM 432 CA PHE A 56 36.699 16.589 7.404 1.00 18. 93 6

ATOM 433 C PHE A 56 37.459 17.589 6.579 1.00 20. 83 6

ATOM 434 O PHE A 56 38.263 17.314 5.680 1.00 21. 50 8

ATOM 435 CB PHE A 56 37.671 15.557 8.060 1.00 17. 73 6

ATOM 436 CG PHE A 56 38.721 16.209 8.950 1.00 19. 66 6

ATOM 437 CDl PHE A 56 38.297 16.881 10.098 1.00 20. 08 6

ATOM 438 CD2 PHE A 56 40.059 16.144 8.616 1.00 20. 24 6

ATOM 439 CEl PHE A 56 39.261 17.479 10.909 1.00 19. 99 6

ATOM 440 CE2 PHE A 56 41.029 16.743 9.433 1.00 20. 35 6

ATOM 441 CZ PHE A 56 40.591 17.409 10.573 1.00 21. 50 6

ATOM 442 N VAL A 57 37.284 18.883 6.949 1.00 21. 60 7

ATOM 443 CA VAL A 57 38.009 19.978 6.334 1.00 23. 17 6

ATOM 444 C VAL A 57 39.362 20.006 7.039 1.00 25. 23 6

ATOM 445 O VAL A 57 39.473 20.469 8.172 1.00 24. 88 8

ATOM 446 CB VAL A 57 37.247 21.325 6.458 1.00 23. 78 6

ATOM 447 CGI VAL A 57 38.051 22.403 5.763 1.00 24. 08 6

ATOM 448 CG2 VAL A 57 35.853 21.178 5.874 1.00 23. 56 6

ATOM 449 N ASN A 58 40.343 19.429 6.377 1.00 24. 28 7

ATOM 450 CA ASN A 58 41.667 19.181 6.907 1.00 22. ,31 6

ATOM 451 C ASN A 58 42.545 20.385 6.858 1.00 23. 05 6

ATOM 452 O ASN A 58 43.072 20.747 5.806 1.00 24. 44 8

ATOM 453 CB ASN A 58 42.250 18.045 6.040 1.00 21. 07 6

ATOM 454 CG ASN A 58 43.684 17.738 6.385 1.00 22. ,18 6

ATOM 455 ODl ASN A 58 44.133 17.942 7.521 1.00 23. ,39 8

ATOM 456 ND2 ASN A 58 44.431 17.254 5.415 1.00 20. ,86 7

ATOM 457 N PRO A 59 42.863 21.002 8.000 1.00 24. ,30 7

ATOM 458 CA PRO A 59 43.727 22.187 7.996 1.00 25. .81 6

ATOM 459 C PRO A 59 45.060 22.042 7.348 1.00 26. .27 6

ATOM 460 O PRO A 59 45.679 22.957 6.784 1.00 27. .28 8

ATOM 461 CB PRO A 59 43.869 22.509 9.493 1.00 24. .50 6

ATOM 462 CG PRO A 59 42.719 21.834 10.171 1.00 26. .42 6

ATOM 463 CD PRO A 59 42.427 20.600 9.337 1.00 24, .44 6

ATOM 464 N MET A 60 45.602 20.784 7.391 1.00 27, .24 7

ATOM 465 CA MET A 60 46.952 20.529 6.856 1.00 28, .64 6

ATOM 466 C MET A 60 47.008 20.656 5.361 1.00 31, .51 6

ATOM 467 O MET A 60 48.101 20.868 4.822 1.00 31 .68 8

ATOM 468 CB MET A 60 47.374 19.171 7.462 1.00 28, .13 6

ATOM 469 CG MET A 60 48.810 18.867 7.264 1.00 32, .00 6

ATOM 470 SD MET A 60 49.373 17.277 7.999 1.00 31 .44 16

ATOM 471 CE MET A 60 50.665 17.068 6.848 1.00 31 .98 6

ATOM 472 N GLN A 61 45.847 20.601 4.648 1.00 30 .53 7

ATOM 473 CA GLN A 61 45.972 20.800 3.202 1.00 33 .22 6

ATOM 474 C GLN A 61 45.492 22.174 2.780 1.00 35 .82 6

ATOM 475 O GLN A 61 45.183 22.463 1.611 1.00 39 .20 8

ATOM 476 CB GLN A 61 45.264 19.567 2.566 1.00 31 .83 6

ATOM 477 CG GLN A 61 43.747 19.745 2.433 1.00 29 .02 6

ATOM 478 CD GLN A 61 43.189 18.320 2.094 1.00 28 .13 6

ATOM 479 OEl GLN A 61 43.302 17.290 2.731 1.00 24 .18 8

ATOM 480 NE2 GLN A 61 42.486 18.326 0.963 1.00 28 .14 7

ATOM 481 N PHE A 62 45.576 23.209 3.658 1.00 33 .24 7

ATOM 482 CA PHE A 62 45.219 24.574 3.275 1.00 33 .76 6

ATOM 483 C PHE A 62 46.434 25.502 3.390 1.00 35 .21 6

ATOM 484 O PHE A 62 47.120 25.382 4.405 1.00 33 .54 8

ATOM 485 CB PHE A 62 44.138 25.218 4.136 1.00 31 .27 6

ATOM 486 CG PHE A 62 42.754 24.742 3.809 1.00 30 .27 6

ATOM 487 CDl PHE A 62 42.301 23.528 4.291 1.00 29 .03 6

ATOM 488 CD2 PHE A 62 41.930 25.486 2.975 1.00 29 .79 6

ATOM 489 CEl PHE A 62 41.037 23.065 3.956 1.00 28 .62 6

ATOM 490 CE2 PHE A 62 40.682 25.043 2.637 1.00 28 .83 6

ATOM 491 CZ PHE A 62 40.223 23.823 3.112 1.00 28 .44 6

ATOM 492 N ASP A 63 46.598 26.394 2.439 1.00 40 .06 7

ATOM 493 CA ASP A 63 47.689 27.339 2.350 1.00 42 .93 6

ATOM 494 C ASP A 63 47.787 28.342 3.485 1.00 44 .06 6

ATOM 495 O ASP A 63 48.906 28.726 3.827 1.00 43 .96 8

ATOM 496 CB ASP A 63 47.575 28.206 1.085 1.00 47 .09 6

ATOM 497 CG ASP A 63 47.423 27.434 -0.198 1.00 51 .39 6

ATOM 498 ODl ASP A 63 47.397 26.169 -0.162 1.00 54 .46 8 ATOM 499 OD2 ASP A 63 47.317 28.098 -1.257 1.00 52.58 8

ATOM 500 N ARG A 64 46.669 28.845 3.990 1.00 43.31 7

ATOM 501 CA ARG A 64 46.717 29.795 5.095 1.00 44.44 6

ATOM 502 C ARG A 64 45.451 2*** 5.923 1.00 41.86 6

ATOM 503 O ARG A 64 44.424 29.201 5.428 1.00 38.21 8

ATOM 504 CB ARG A 64 46.808 31.240 4.660 1.00 47.55 6

ATOM 505 CG ARG A 64 48.161 31.803 4.295 1.00 52.46 6

ATOM 506 CD ARG A 64 47.938 33.125 3.520 1.00 55.58 6

ATOM 507 NE ARG A 64 47.067 32.875 2.441 1.00 58.62 7

ATOM 508 CZ ARG A 64 46.215 32.846 1.486 1.00 60.36 6

ATOM 509 NHl ARG A 64 45.436 33.900 1.230 1.00 62.10 7

ATOM 510 NH2 ARG A 64 46.118 31.748 0.742 1.00 60.56 7

ATOM 511 N PRO A 65 45.506 30.080 7.169 1.00 41.07 7

ATOM 512 CA PRO A 65 44.375 30.002 8.068 1.00 41.23 6

ATOM 513 C PRO A 65 43.127 30.709 7.584 1.00 41.03 6

ATOM 514 O PRO A 65 42.000 30.258 7.847 1.00 39.31 8

ATOM 515 CB PRO A 65 44.911 30.622 9.356 1.00 42.70 6

ATOM 516 CG PRO A 65 46.398 30.368 9.281 1.00 43.00 6

ATOM 517 CD PRO A 65 46.709 30.642 7.823 1.00 42.34 6

ATOM 518 N GLU A 66 43.274 31.789 6.810 1.00 41.59 7

ATOM 519 CA GLU A 66 42.070 32.514 6.362 1.00 42.96 6

ATOM 520 C GLU A 66 41.347 31.757 5.259 1.00 40.61 6

ATOM 521 O GLU A 66 40.120 31.853 5.153 1.00 38.18 8

ATOM 522 CB GLU A 66 42.463 33.934 5.932 1.00 48.02 6

ATOM 523 CG GLU A 66 43.670 33.931 5.016 1.00 54.67 6

ATOM 524 CD GLU A 66 44.083 35.290 4.503 1.00 59.02 6

ATOM 525 OE1 GLU A 66 44.156 36.244 5.323 1.00 62.04 8

ATOM 526 OE2 GLU A 66 44.334 35.389 3.276 1.00 60.81 8

ATOM 527 N ASP A 67 42.108 30.969 4.481 1.00 38.50 7

ATOM 528 CA ASP A 67 41.447 30.178 3.439 1.00 37.14 6

ATOM 529 C ASP A 67 40.655 29.082 4.122 1.00 34.07 6

ATOM 530 O ASP A 67 39.529 28.761 3.792 1.00 30.58 8

ATOM 531 CB ASP A 67 42.413 29.550 2.449 1.00 41.16 6

ATOM 532 CG ASP A 67 43.388 30.540 1.846 1.00 44.61 6

ATOM 533 ODl ASP A 67 43.068 31.742 1.741 1.00 46.57 8

ATOM 534 OD2 ASP A 67 44.487 30.073 1.482 1.00 47.46 8

ATOM 535 N LEU A 68 41.286 28.452 5.142 1.00 31.94 7

ATOM 536 CA LEU A 68 40.581 27.433 5.887 1.00 30.62 6

ATOM 537 C LEU A 68 39.303 27.981 6.477 1.00 30.54 6

ATOM 538 O LEU A 68 38.243 27.345 6.533 1.00 30.35 8

ATOM 539 CB LEU A 68 41.523 26.893 7.001 1.00 29.74 6

ATOM 540 CG LEU A 68 40.908 25.958 8.016 1.00 30.11 6

ATOM 541 CDl LEU A 68 40.510 24.577 7.474 1.00 30.95 6

ATOM 542 CD2 LEU A 68 41.899 25.712 9.149 1.00 31.60 6

ATOM 543 N ALA A 69 39.345 29.225 7.012 1.00 29.90 7

ATOM 544 CA ALA A 69 38.146 29.740 7.662 1.00 32.87 6

ATOM 545 C ALA A 69 37.021 29.993 6.663 1.00 34.82 6

ATOM 546 O ALA A 69 35.855 29.854 7.018 1.00 35.59 8

ATOM 547 CB ALA A 69 38.487 31.030 8.425 1.00 32.66 6

ATOM 548 N ARG A 70 37.345 30.321 5.431 1.00 34.63 7

ATOM 549 CA ARG A 70 36.337 30.625 4.423 1.00 37.34 6

ATOM 550 C ARG A 70 35.777 29.350 3.803 1.00 36.74 6

ATOM 551 O ARG A 70 34.726 29.502 3.165 1.00 35.73 8

ATOM 552 CB ARG A 70 36.923 31.526 3.334 1.00 38.93 6

ATOM 553 CG ARG A 70 37.284 32.923 3.813 1.00 41.54 6

ATOM 554 CD ARG A 70 37.555 33.855 2.643 1.00 43.19 6

ATOM 555 NE ARG A 70 38.731 33.447 1.880 1.00 47.13 7

ATOM 556 CZ ARG A 70 39.977 33.789 2.190 1.00 47.82 6

ATOM 557 NHl ARG A 70 40.213 34.544 3.252 1.00 51.37 7

ATOM 558 NH2 ARG A 70 40.984 33.371 1.435 1.00 48.98 7

ATOM 559 N TYR A 71 36.419 28.197 3.875 1.00 32.87 7

ATOM 560 CA TYR A 71 35.941 26.999 3.187 1.00 31.99 6

ATOM 561 C TYR A 71 34.522 26.700 3.578 1.00 30.54 6

ATOM 562 O TYR A 71 34.125 26.714 4.739 1.00 30.28 8

ATOM 563 CB TYR A 71 36.927 25.840 3.502 1.00 29.15 6

ATOM 564 CG TYR A 71 36.753 24.730 2.482 1.00 29.96 6

ATOM 565 CDl TYR A 71 37.363 24.753 1.233 1.00 30.99 6

ATOM 566 CD2 TYR A 71 35.931 23.658 2.815 1.00 29.82 6

ATOM 567 CEl TYR A 71 37.166 23.667 0.356 1.00 33.09 6

ATOM 568 CE2 TYR A 71 35.713 22.625 1.927 1.00 31.04 6

ATOM 569 CZ TYR A 71 36.332 22.650 0.702 1.00 31.47 6

ATOM 570 OH TYR A 71 36.163 21.647 -0.214 1.00 34.74 8

ATOM 571 N PRO A 72 33.687 26.356 2.591 1.00 33.76 7

ATOM 572 CA PRO A 72 32.271 26.095 2.809 1.00 35.62 6 ATOM 573 C PRO A 72 31.987 24.932 3.712 1.00 36.23 6

ATOM 574 O PRO A 72 32.552 23.855 3.521 1.00 37.45 8

ATOM 575 CB PRO A 72 31.695 25.904 1.408 1.00 36.05 6

ATOM 576 CG PRO A 72 32.853 25.628 0.524 1.00 36.68 6

ATOM 577 CD PRO A 72 34.044 26.284 1.155 1.00 35.26 6

ATOM 578 N ARG A 73 31.114 25.089 4.705 1.00 35.24 7

ATOM 579 CA ARG A 73 30.752 23.978 5.580 1.00 35.44 6

ATOM 580 C ARG A 73 29.254 23.808 5.446 1.00 36.32 6

ATOM 581 O ARG A 73 28.544 24.827 5.569 1.00 36.64 8

ATOM 582 CB ARG A 73 31.232 24.214 7.012 1.00 37.96 6

ATOM 583 CG ARG A 73 32.778 24.055 6.985 1.00 38.27 6

ATOM 584 CD ARG A 73 33.433 24.599 8.180 1.00 39.86 6

ATOM 585 NE ARG A 73 34.854 24.417 8.347 1.00 37.69 7

ATOM 586 CZ ARG A 73 35.799 25.216 7.876 1.00 38.63 6

ATOM 587 NHl ARG A 73 37.047 24.918 8.212 1.00 36.16 7

ATOM 588 NH2 ARG A 73 35.534 26.279 7.132 1.00 38.20 7

ATOM 589 N THR A 74 28.763 22.645 5.057 1.00 34.43 7

ATOM 590 CA THR A 74 27.358 22.363 4.859 1.00 34.04 6

ATOM 591 C THR A 74 27.033 20.953 5.354 1.00 32.80 6

ATOM 592 O THR A 74 26.421 20.107 4.689 1.00 31.08 8

ATOM 593 CB THR A 74 26.856 22.409 3.403 1.00 36.39 6

ATOM 594 OG1 THR A 74 27.567 21.394 2.652 1.00 38.24 8

ATOM 595 CG2 THR A 74 27.020 23.800 2.776 1.00 37.30 6

ATOM 596 N LEU A 75 27.405 20.714 6.616 1.00 31.90 7

ATOM 597 CA LEU A 75 27.234 19.377 7.168 1.00 30.80 6

ATOM 598 C LEU A 75 25.818 18.900 7.129 1.00 30.32 6

ATOM 599 O LEU A 75 25.595 17.716 6.815 1.00 29.31 8

ATOM 600 CB LEU A 75 27.865 19.401 8.605 1.00 32.17 6

ATOM 601 CG LEU A 75 27.986 18.001 9.219 1.00 33.15 6

ATOM 602 CDl LEU A 75 28.985 17.154 8.420 1.00 33.59 6

ATOM 603 CD2 LEU A 75 28.401 18.093 10.663 1.00 32.87 6

ATOM 604 N GLN A 76 24.793 19.692 7.502 1.00 29.90 7

ATOM 605 CA GLN A 76 23.429 19.175 7.436 1.00 31.72 6

ATOM 606 C GLN A 76 23.040 18.695 6.054 1.00 28.82 6

ATOM 607 O GLN A 76 22.449 17.626 5.924 1.00 30.69 8

ATOM 608 CB GLN A 76 22.423 20.270 7.881 1.00 34.78 6

ATOM 609 CG GLN A 76 21.016 19.720 8.042 1.00 40.38 6

ATOM 610 CD GLN A 76 20.095 20.836 8.524 1.00 45.28 6

ATOM 611 OE1 GLN A 76 19.111 21.196 7.859 1.00 48.24 8

ATOM 612 NE2 GLN A 76 20.453 21.402 9.677 1.00 47.35 7

ATOM 613 N GLU A 77 23.274 19.493 5.023 1.00 26.49 7

ATOM 614 CA GLU A 77 22.946 19.111 3.656 1.00 27.35 6

ATOM 615 C GLU A 77 23.777 17.906 3.193 1.00 27.59 6

ATOM 616 O GLU A 77 23.263 17.064 2.463 1.00 27.03 8

ATOM 617 CB GLU A 77 23.227 20.280 2.718 1.00 28.83 6

ATOM 618 CG GLU A 77 22.722 19.997 1.302 1.00 32.09 6

ATOM 619 N ASP A 78 25.048 17.886 3.617 1,00 26.66 7

ATOM 620 CA ASP A 78 25.875 16.706 3.239 1.00 26.91 6

ATOM 621 C ASP A 78 25.226 15.431 3.735 1.00 26.68 6

ATOM 622 O ASP A 78 25.042 14.448 3.018 1.00 24.38 8

ATOM 623 CB ASP A 78 27.275 16.820 3.796 1.00 25.18 6

ATOM 624 CG ASP A 78 28.116 17.931 3.332 1.00 28.50 6

ATOM 625 ODl ASP A 78 27.681 18.573 2.312 1.00 28.92 8

ATOM 626 OD2 ASP A 78 29.179 18.397 3.774 1.00 29.90 8

ATOM 627 N CYS A 79 24.883 15.488 5.051 1.00 27.85 7

ATOM 628 CA CYS A 79 24.304 14.292 5.666 1.00 30.04 6

ATOM 629 C CYS A 79 22.949 13.894 5.111 1.00 29.71 6

ATOM 630 O CYS A 79 22.684 12.715 4.944 1.00 29.58 8

ATOM 631 CB CYS A 79 24.188 14.507 7.183 1.00 31.67 6

ATOM 632 SG CYS A 79 25.844 14.386 7.916 1.00 33.92 16

ATOM 633 N GLU A 80 22.134 14.874 4.734 1.00 30.93 7

ATOM 634 CA GLU A 80 20.899 14.555 4.007 1.00 32.01 6

ATOM 635 C GLU A 80 21.197 13.812 2.705 1.00 29.17 6

ATOM 636 O GLU A 80 20.524 12.822 2.413 1.00 29.08 8

ATOM 637 CB GLU A 80 20.135 15.852 3.756 1.00 36.34 6

ATOM 638 CG GLU A 80 19.379 16.349 4.985 1.00 43.73 6

ATOM 639 CD GLU A 80 18.700 17.700 4.818 1.00 48.86 6

ATOM 640 OE1 GLU A 80 18.432 18.156 3.670 1.00 51.62 8

ATOM 641 OE2 GLU A 80 18.442 18.338 5.884 1.00 51.33 8

ATOM 642 N LYS A 81 22.175 14.264 1.921 1.00 26.79 7

ATOM 643 CA LYS A 81 22.522 13.581 0.676 1.00 27.73 6

ATOM 644 C LYS A 81 23.067 12.161 0.921 1.00 27.62 6

ATOM 645 O LYS A 81 22.686 11.291 0.147 1.00 25.90 8

ATOM 646 CB LYS A 81 23.541 14.390 -0.112 1.00 27.61 6 ATOM 647 CG LYS A 81 23.036 15.708 -0.702 1.00 27.05 6

ATOM 648 CD LYS A 81 24.149 16.381 -1.485 1.00 29.23 6

ATOM 649 CE LYS A 81 23.586 17.726 -1.958 1.00 31.40 6

ATOM 650 NZ LYS A 81 24.290 18.189 -3.180 1.00 33.21 7

ATOM 651 N LEU A 82 23.941 12.067 1.932 1.00 25.01 7

ATOM 652 CA LEU A 82 24.428 10.653 2.208 1.00 25.50 6

ATOM 653 C LEU A 82 23.359 9.729 2.719 1.00 24.46 6

ATOM 654 O LEU A 82 23.296 8.571 2.335 1.00 25.35 8

ATOM 655 CB LEU A 82 25.616 10.767 3.179 1.00 24.87 6

ATOM 656 CG LEU A 82 26.765 11.600 2.627 1.00 25.74 6

ATOM 657 CDl LEU A 82 27.854 11.923 3.663 1.00 24.08 6

ATOM 658 CD2 LEU A 82 27.412 10.853 1.463 1.00 24.64 6

ATOM 659 N ASN A 83 22.437 10.262 3.549 1.00 27.59 7

ATOM 660 CA ASN A 83 21.352 9.467 4.081 1.00 29.62 6

ATOM 661 C ASN A 83 20.400 9.086 2.941 1.00 31.66 6

ATOM 662 O ASN A 83 20.066 7.899 2.966 1.00 31.60 8

ATOM 663 CB ASN A 83 20.649 10.212 5.205 1.00 32.77 6

ATOM 664 CG ASN A 83 19.718 9.324 6.010 1.00 37.49 6

ATOM 665 ODl ASN A 83 18.788 9.898 6.588 1.00 42.54 8

ATOM 666 ND2 ASN A 83 19.899 8.019 6.093 1.00 37.69 7

ATOM 667 N LYS A 84 20.176 9.954 1.933 1.00 31.56 7

ATOM 668 CA LYS A 84 19.397 9.440 0.781 1.00 33.04 6

ATOM 669 C LYS A 84 20.155 8.440 -0.069 1.00 34.14 6

ATOM 670 O LYS A 84 19.531 7.661 -0.824 1.00 34.69 8

ATOM 671 CB LYS A 84 18.915 10.637 -0.071 1.00 36.71 6

ATOM 672 CG LYS A 84 17.639 11.350 0.339 1.00 42.14 6

ATOM 673 CD LYS A 84 17.457 12.707 -0.355 1.00 45.16 6

ATOM 674 CE LYS A 84 16.334 13.494 0.303 1.00 48.19 6

ATOM 675 NZ LYS A 84 16.337 14.928 -0.105 1.00 50.51 7

ATOM 676 N ARG A 85 21.483 8.305 0.021 1.00 34.32 7

ATOM 677 CA ARG A 85 22.276 7.344 -0.773 1.00 33.70 6

ATOM 678 C ARG A 85 22.620 6.057 -0.050 1.00 34.60 6

ATOM 679 O ARG A 85 23.358 5.112 -0.377 1.00 36.33 8

ATOM 680 CB ARG A 85 23.529 8.099 -1.166 1.00 34.84 6

ATOM 681 CG ARG A 85 24.040 7.946 -2.583 1.00 36.24 6

ATOM 682 CD ARG A 85 23.177 8.780 -3.502 1.00 37.79 6

ATOM 683 NE ARG A 85 23.549 8.555 -4.891 1.00 36.63 7

ATOM 684 CZ ARG A 85 23.122 9.364 -5.853 1.00 37.76 6

ATOM 685 NHl ARG A 85 22.368 10.397 -5.507 1.00 38.88 7

ATOM 686 NH2 ARG A 85 23.473 9.117 -7.100 1.00 37.39 7

ATOM 687 N LYS A 86 21.948 5.940 1.093 1.00 33.51 7

ATOM 688 CA LYS A 86 21.983 4.881 2.059 1.00 34.48 6

ATOM 689 C LYS A 86 23.404 4.563 2.503 1.00 32.25 6

ATOM 690 O LYS A 86 23.823 3.405 2.516 1.00 34.37 8

ATOM 691 CB LYS A 86 21.290 3.624 1.477 1.00 37.47 6

ATOM 692 CG LYS A 86 19.862 3.957 1.034 1.00 42.40 6

ATOM 693 CD LYS A 86 18.990 4.373 2.205 1.00 46.88 6

ATOM 694 CE LYS A 86 18.857 3.256 3.233 1.00 50.03 6

ATOM 695 NZ LYS A 86 18.397 3.827 4.543 1.00 52.47 7

ATOM 696 N VAL A 87 24.138 5.595 2.885 1.00 29.97 7

ATOM 697 CA VAL A 87 25.490 5.405 3.428 1.00 26.05 6

ATOM 698 C VAL A 87 25.390 4.849 4.829 1.00 28.43 6

ATOM 699 O VAL A 87 24.498 5.233 5.587 1.00 26.14 8

ATOM 700 CB VAL A 87 26.199 6.749 3.397 1.00 26.58 6

ATOM 701 CGI VAL A 87 27.425 6.848 4.304 1.00 23.69 6

ATOM 702 CG2 VAL A 87 26.640 7.063 1.961 1.00 25.53 6

ATOM 703 N ASP A 88 26.274 3.947 5.231 1.00 25.06 7

ATOM 704 CA ASP A 88 26.163 3.320 6.552 1.00 27.11 6

ATOM 705 C ASP A 88 26.718 4.129 7.696 1.00 26.68 6

ATOM 706 O ASP A 88 26.108 4,221 8.763 1.00 27.00 8

ATOM 707 CB ASP A 88 26.899 1.986 6.461 1.00 29.00 6

ATOM 708 CG ASP A 88 26.332 1.114 5.377 1.00 31.90 6

ATOM 709 ODl ASP A 88 25.301 0.444 5.714 1.00 34.25 8

ATOM 710 OD2 ASP A 88 26.819 1.060 4.237 1.00 30.16 8

ATOM 711 N LEU A 89 27.798 4.864 7.483 1.00 21.05 7

ATOM 712 CA LEU A 89 28.448 5.620 8.532 1.00 22.89 6

ATOM 713 C LEU A 89 29.085 6.879 7.997 1.00 25.24 6

ATOM 714 O LEU A 89 29.775 6.771 6.967 1.00 24.36 8

ATOM 715 CB LEU A 89 29.561 4.723 9.069 1.00 27.61 6

ATOM 716 CG LEU A 89 30.275 5.099 10.342 1.00 31.35 6

ATOM 717 CDl LEU A 89 30.916 3.857 10.963 1.00 34.98 6

ATOM 718 CD2 LEU A 89 31.363 6.137 10.099 1.00 33.01 6

ATOM 719 N VAL A 90 28.910 7.987 8.677 1.00 22.49 7

ATOM 720 CA VAL A 90 29.577 9.200 8.296 1.00 23.34 6 ATOM 721 C VAL A 90 30.551 9.518 9.431 1.00 24.94 6

ATOM 722 O VAL A 90 30.041 9.581 10.575 1.00 25.44 8

ATOM 723 CB VAL A 90 28.602 10.366 8.153 1.00 21.61 6

ATOM 724 CGI VAL A 90 29.294 11.692 7.966 1.00 23.24 6

ATOM 725 CG2 VAL A 90 27.695 10.065 6.945 1.00 24.01 6

ATOM 726 N PHE A 91 31.819 9.736 9.120 1.00 20.62 7

ATOM 727 CA PHE A 91 32.779 10.106 10.131 1.00 21.25 6

ATOM 728 C PHE A 91 33.008 11.589 9.966 1.00 22.65 6

ATOM 729 O PHE A 91 33.612 12.028 8.957 1.00 20.89 8

ATOM 730 CB PHE A 91 34.059 9.254 9.968 1.00 20.01 6

ATOM 731 CG PHE A 91 35.181 9.639 10.897 1.00 20.02 6

ATOM 732 CDl PHE A 91 34.954 9.716 12.277 1.00 20.82 6

ATOM 733 CD2 PHE A 91 36.465 9.830 10.421 1.00 21.38 6

ATOM 734 CEl PHE A 91 36.004 10.045 13.150 1.00 21.05 6

ATOM 735 CE2 PHE A 91 37.503 10.196 11.281 1.00 23.76 6

ATOM 736 CZ PHE A 91 37.261 10.233 12.631 1.00 21.99 6

ATOM 737 N ALA A 92 32.580 12.382 10.985 1.00 23.09 7

ATOM 738 CA ALA A 92 32.750 13.824 10.898 1.00 23.04 6

ATOM 739 C ALA A 92 33.406 14.387 12.142 1.00 24.15 6

ATOM 740 O ALA A 92 32.699 14.986 12.979 1.00 24.45 8

ATOM 741 CB ALA A 92 31.368 14.496 10.717 1.00 23.41 6

ATOM 742 N PRO A 93 34.701 14.252 12.284 1.00 23.10 7

ATOM 743 CA PRO A 93 35.387 14.638 13.507 1.00 21.87 6

ATOM 744 C PRO A 93 35.695 16.093 13.560 1.00 23.67 6

ATOM 745 O PRO A 93 35.740 16.790 12.510 1.00 24.71 8

ATOM 746 CB PRO A 93 36.687 13.798 13.426 1.00 21.94 6

ATOM 747 CG PRO A 93 37.002 13.904 11.930 1.00 23.58 6

ATOM 748 CD PRO A 93 35.643 13.553 11.336 1.00 21.29 6

ATOM 749 N SER A 94 35.940 16.664 14.752 1.00 23.63 7

ATOM 750 CA SER A 94 36.447 18.022 14.812 1.00 26.17 6

ATOM 751 C SER A 94 37.939 18.117 14.561 1.00 26.12 6

ATOM 752 O SER A 94 38.700 17.126 14.588 1.00 25.24 8

ATOM 753 CB SER A 94 36.151 18.617 16.207 1.00 26.90 6

ATOM 754 OG SER A 94 36.930 17.871 17.168 1.00 27.23 8

ATOM 755 N VAL A 95 38.487 19.308 14.308 1.00 25.69 7

ATOM 756 CA VAL A 95 39.900 19.519 14.115 1.00 25.50 6

ATOM 757 C VAL A 95 40.639 19.107 15.409 1.00 28.17 6

ATOM 758 O VAL A 95 41.692 18.475 15.307 1.00 27.54 8

ATOM 759 CB VAL A 95 40.319 20.963 13.788 1.00 27.40 6

ATOM 760 CGI VAL A 95 41.808 21.236 13.929 1.00 27.91 6

ATOM 761 CG2 VAL A 95 39.873 21.263 12.346 1.00 26.36 6

ATOM 762 N LYS A 96 40.047 19.405 16.570 1.00 26.82 7

ATOM 763 CA LYS A 96 40.718 18.994 17.823 1.00 28.89 6

ATOM 764 C LYS A 96 40.773 17.474 17.962 1.00 28.61 6

ATOM 765 O LYS A 96 41.723 16.951 18.539 1.00 27.95 8

ATOM 766 CB LYS A 96 40.013 19.550 19.066 1.00 29.19 6

ATOM 767 N GLU A 97 39.756 16.765 17.486 1.00 28.36 7

ATOM 768 CA GLU A 97 39.748 15.295 17.583 1.00 29.80 6

ATOM 769 C GLU A 97 40.830 14.674 16.708 1.00 29.13 6

ATOM 770 O GLU A 97 41.565 13.752 17.126 1.00 29.24 8

ATOM 771 CB GLU A 97 38.365 14.782 17.214 1.00 29.05 6

ATOM 772 CG GLU A 97 38.194 13.265 17.303 1.00 28.83 6

ATOM 773 CD GLU A 97 38.133 12.796 18.762 1.00 30.81 6

ATOM 774 OE1 GLU A 97 38.046 13.687 19.649 1.00 32.00 8

ATOM 775 OE2 GLU A 97 38.132 11.592 19.080 1.00 28.32 8

ATOM 776 N ILE A 98 41.066 15.194 15.516 1.00 26.74 7

ATOM 777 CA ILE A 98 42.110 14.673 14.641 1.00 24.88 6

ATOM 778 C ILE A 98 43.483 15.219 14.955 1.00 26.67 6

ATOM 779 O ILE A 98 44.485 14.459 14.852 1.00 24.09 8

ATOM 780 CB ILE A 98 41.817 14.972 13.147 1.00 23.79 6

ATOM 781 CGI ILE A 98 40.483 14.337 12.789 1.00 22.35 6

ATOM 782 CG2 ILE A 98 42.971 14.486 12.252 1.00 22.39 6

ATOM 783 CDl ILE A 98 40.431 12.804 12.865 1.00 24.57 6

ATOM 784 N TYR A 99 43.603 16.493 15.375 1.00 24.39 7

ATOM 785 CA TYR A 99 44.886 17.127 15.585 1.00 26.57 6

ATOM 786 C TYR A 99 44.917 17.788 16.978 1.00 26.98 6

ATOM 787 O TYR A 99 44.959 18.984 17.080 1.00 29.92 8

ATOM 788 CB TYR A 99 45.244 18.185 14.514 1.00 24.58 6

ATOM 789 CG TYR A 99 45.318 17.673 13.080 1.00 24.59 6

ATOM 790 CDl TYR A 99 44.461 18.086 12.085 1.00 23.63 6

ATOM 791 CD2 TYR A 99 46.371 16.838 12.709 1.00 23.01 6

ATOM 792 CEl TYR A 99 44.573 17.677 10.760 1.00 23.55 6

ATOM 793 CE2 TYR A 99 46.491 16.358 11.405 1.00 25.75 6

ATOM 794 CZ TYR A 99 45.593 16.773 10.447 1.00 24.33 6 o o ca

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ATOM 869 C VAL A 109 53.653 12.022 3.954 1.00 24.73 6

ATOM 870 O VAL A 109 52.756 12.811 3.553 1.00 23.81 8

ATOM 871 CB VAL A 109 52.263 10.230 4.964 1.00 20.04 6

ATOM 872 CGI VAL A 109 52.619 9.362 3.731 1.00 23.57 6

ATOM 873 CG2 VAL A 109 51.946 9.420 6.209 1.00 17.72 6

ATOM 874 N ASP A 110 54.753 11.885 3.237 1.00 25.18 7

ATOM 875 CA ASP A 110 55.054 12.663 2.047 1.00 28.26 6

ATOM 876 C ASP A 110 55.453 11.784 0.881 1.00 25.00 6

ATOM 877 O ASP A 110 56.220 10.815 1.006 1.00 23.50 8

ATOM 878 CB ASP A 110 56.199 13.596 2.383 1.00 34.46 6

ATOM 879 CG ASP A 110 56.031 15.027 1.970 1.00 42.11 6

ATOM 880 ODl ASP A 110 56.945 15.774 2.403 1.00 48.30 8

ATOM 881 OD2 ASP A 110 55.098 15.496 1.290 1.00 46.79 8

ATOM 882 N VAL A 111 54.851 11.964 -0.272 1.00 24.14 7

ATOM 883 CA VAL A 111 55.111 11.236 -1.493 1.00 23.80 6

ATOM 884 C VAL A 111 56.023 12.085 -2.363 1.00 24.56 6

ATOM 885 O VAL A 111 55.572 13.037 -3.027 1.00 25.12 8

ATOM 886 CB VAL A 111 53.771 10.929 -2.218 1.00 23.25 6

ATOM 887 CGI VAL A 111 54.020 10.068 -3.456 1.00 22.00 6

ATOM 888 CG2 VAL A 111 52.810 10.285 -1.246 1.00 22.35 6

ATOM 889 N PRO A 112 57.278 11.687 -2.453 1.00 26.28 7

ATOM 890 CA PRO A 112 58.274 12.438 -3.222 1.00 27.97 6

ATOM 891 C PRO A 112 57.906 12.619 -4.650 1.00 30.72 6

ATOM 892 O PRO A 112 57.272 11.711 -5.253 1.00 30.37 8

ATOM 893 CB PRO A 112 59.532 11.573 -3.106 1.00 27.29 6

ATOM 894 CG PRO A 112 59.413 10.926 -1.769 1.00 27.60 6

ATOM 895 CD PRO A 112 57.905 10.536 -1.762 1.00 24.64 6

ATOM 896 N GLY A 113 58.211 13.800 -5.209 1.00 30.66 7

ATOM 897 CA GLY A 113 57.940 14.000 -6.614 1.00 32.72 6

ATOM 898 C GLY A 113 56.543 14.464 -6.926 1.00 31.39 6

ATOM 899 O GLY A 113 56.346 15.614 -7.280 1.00 30.61 8

ATOM 900 N LEU A 114 55.558 13.575 -6.772 1.00 27.67 7

ATOM 901 CA LEU A 114 54.192 13.922 -7.023 1.00 28.50 6

ATOM 902 C LEU A 114 53.677 15.086 -6.186 1.00 29.37 6

ATOM 903 O LEU A 114 52.810 15.829 -6.657 1.00 33.05 8

ATOM 904 CB LEU A 114 53.283 12.710 -6.702 1.00 29.66 6

ATOM 905 CG LEU A 114 53.515 11.551 -7.669 1.00 31.75 6

ATOM 906 CDl LEU A 114 52.703 10.351 -7.233 1.00 31.73 6

ATOM 907 CD2 LEU A 114 53.134 11.977 -9.059 1.00 35.50 6

ATOM 908 N SER A 115 54.161 15.180 -4.965 1.00 26.50 7

ATOM 909 CA SER A 115 53.664 16.206 -4.063 1.00 27.52 6

ATOM 910 C SER A 115 54.245 17.582 -4.400 1.00 30.00 6

ATOM 911 O SER A 115 53.590 18.536 -3.932 1.00 28.18 8

ATOM 912 CB SER A 115 53.978 15.885 -2.599 1.00 25.46 6

ATOM 913 OG SER A 115 55.407 15.846 -2.464 1.00 30.73 8

ATOM 914 N THR A 116 55.312 17.617 -5.177 1.00 30.25 7

ATOM 915 CA THR A 116 55.884 18.969 -5.426 1.00 32.64 6

ATOM 916 C THR A 116 55.854 19.345 -6.870 1.00 33.28 6

ATOM 917 O THR A 116 56.516 20.337 -7.260 1.00 37.48 8

ATOM 918 CB THR A 116 57.318 19.018 -4.839 1.00 31.68 6

ATOM 919 OG1 THR A 116 58.066 17.923 -5.419 1.00 33.81 8

ATOM 920 CG2 THR A 116 57.348 18.863 -3.344 1.00 30.91 6

ATOM 921 N MET A 117 55.075 18.691 -7.725 1.00 34.70 7

ATOM 922 CA MET A 117 54.978 19.104 -9.116 1.00 36.76 6

ATOM 923 C MET A 117 53.599 19.679 -9.408 1.00 35.12 6

ATOM 924 O MET A 117 52.722 19.561 -8.569 1.00 34.04 8

ATOM 925 CB MET A 117 55.258 17.952 -10.067 1.00 38.70 6

ATOM 926 CG MET A 117 54.494 16.690 -9.707 1.00 41.51 6

ATOM 927 SD MET A 117 55.327 15.244 -10.403 1.00 45.13 16

ATOM 928 CE MET A 117 55.643 15.848 -12.065 1.00 43.90 6

ATOM 929 N LEU A 118 53.449 20.272 -10.578 1.00 35.18 7

ATOM 930 CA LEU A 118 52.173 20.846 -10.995 1.00 36.73 6

ATOM 931 C LEU A 118 51.570 21.660 -9.877 1.00 36.48 6

ATOM 932 O LEU A 118 52.236 22.552 -9.330 1.00 36.60 8

ATOM 933 CB LEU A 118 51.252 19.706 -11.478 1.00 38.22 6

ATOM 934 CG LEU A 118 51.872 18.829 -12.571 1.00 39.36 6

ATOM 935 CDl LEU A 118 51.001 17.679 -13.051 1.00 41.36 6

ATOM 936 CD2 LEU A 118 52.194 19.710 -13.783 1.00 41.80 6

ATOM 937 N GLU A 119 50.329 21.339 -9.481 1.00 38.80 7

ATOM 938 CA GLU A 119 49.645 22.049 -8.411 1.00 37.83 6

ATOM 939 C GLU A 119 50.401 22.088 -7.102 1.00 38.27 6

ATOM 940 O GLU A 119 50.416 23.101 -6.393 1.00 38.36 8

ATOM 941 CB GLU A 119 48.255 21.394 -8.141 1.00 41.10 6

ATOM 942 CG GLU A 119 47.470 22.109 -7.049 1.00 41.69 6 ATOM 943 CD GLU A 119 46.082 21.559 -6.784 1.00 44.93 6

ATOM 944 OE1 GLU A 119 45.654 20.593 -7.453 1.00 40.85 8

ATOM 945 OE2 GLU A 119 45.379 22.098 -5.892 1.00 45.21 8

ATOM 946 N GLY A 120 51.165 21.031 -6.805 1.00 35.61 7

ATOM 947 CA GLY A 120 51.945 20.951 -5.595 1.00 33.60 6

ATOM 948 C GLY A 120 53.033 22.013 -5.540 1.00 34.42 6

ATOM 949 O GLY A 120 53.390 22.405 -4.437 1.00 36.33 8

ATOM 950 N ALA A 121 53.588 22.394 -6.677 1.00 35.01 7

ATOM 951 CA ALA A 121 54.622 23.437 -6.741 1.00 35.93 6

ATOM 952 C ALA A 121 54.069 24.789 -6.295 1.00 39.30 6

ATOM 953 O ALA A 121 54.752 25.536 -5.588 1.00 40.98 8

ATOM 954 CB ALA A 121 55.189 23.547 -8.150 1.00 32.29 6

ATOM 955 N SER A 122 52.818 25.124 -6.644 1.00 41.40 7

ATOM 956 CA SER A 122 52.261 26.415 -6.226 1.00 44.40 6

ATOM 957 C SER A 122 51.626 26.354 -4.849 1.00 45.24 6

ATOM 958 O SER A 122 51.056 27.328 -4.339 1.00 44.99 8

ATOM 959 CB SER A 122 51.226 26.909 -7.241 1.00 45.02 6

ATOM 960 OG SER A 122 50.178 25.972 -7.432 1.00 46.98 8

ATOM 961 N ARG A 123 51.634 25.169 -4.197 1.00 45.65 7

ATOM 962 CA ARG A 123 51.045 24.991 -2.876 1.00 44.81 6

ATOM 963 C ARG A 123 51.908 24.083 -2.006 1.00 44.93 6

ATOM 964 O ARG A 123 51.557 22.916 -1.788 1.00 44.88 8

ATOM 965 CB ARG A 123 49.631 24.419 -2.992 1.00 45.81 6

ATOM 966 CG ARG A 123 48.629 25.367 -3.630 1.00 46.85 6

ATOM 967 CD ARG A 123 47.248 24.736 -3.714 1.00 50.24 6

ATOM 968 NE ARG A 123 46.466 24.971 -2.504 1.00 52.21 7

ATOM 969 CZ ARG A 123 45.271 24.437 -2.271 1.00 52.64 6

ATOM 970 NHl ARG A 123 44.718 23.633 -3.169 1.00 52.96 7

ATOM 971 NH2 ARG A 123 44.633 24.708 -1.141 1.00 53.34 7

ATOM 972 N PRO A 124 52.717 24.827 -1.604 1.00 44.27 7

ATOM 973 CA PRO A 124 53.669 24.219 -0.725 1.00 43.54 6

ATOM 974 C PRO A 124 53.075 23.501 0.473 1.00 43.43 6

ATOM 975 O PRO A 124 52.427 24.264 1.223 1.00 44.21 8

ATOM 976 CB PRO A 124 54.534 25.391 -0.224 1.00 43.61 6

ATOM 977 CG PRO A 124 54.396 26.439 -1.257 1.00 44.17 6

ATOM 978 CD PRO A 124 52.971 26.302 -1.746 1.00 44.92 6

ATOM 979 N GLY A 125 53.248 21.897 0.840 1.00 39.19 7

ATOM 980 CA GLY A 125 52.585 21.453 2.061 1.00 34.50 6

ATOM 981 C GLY A 125 51.230 20.789 1.809 1.00 32.64 6

ATOM 982 O GLY A 125 50.689 20.112 2.669 1.00 32.97 8

ATOM 983 N HIS A 126 50.594 21.246 0.725 1.00 29.92 7

ATOM 984 CA HIS A 126 49.259 20.776 0.381 1.00 29.41 6

ATOM 985 C HIS A 126 49.186 19.276 0.256 1.00 29.27 6

ATOM 986 O HIS A 126 48.500 18.637 1.071 1.00 29.29 8

ATOM 987 CB HIS A 126 48.782 21.451 -0.934 1.00 29.82 6

ATOM 988 CG HIS A 126 47.453 20.951 -1.417 1.00 30.87 6

ATOM 989 ND1 HIS A 126 46.254 21.263 -0.790 1.00 32.42 7

ATOM 990 CD2 HIS A 126 47.135 20.149 -2.435 1.00 30.12 6

ATOM 991 CEl HIS A 126 45.274 20.643 -1.373 1.00 30.81 6

ATOM 992 NE2 HIS A 126 45.765 19.970 -2.384 1.00 33.87 7

ATOM 993 N PHE A 127 49.882 18.662 -0.698 1.00 25.60 7

ATOM 994 CA PHE A 127 49.770 17.232 -0.922 1.00 25.14 6

ATOM 995 C PHE A 127 50.320 16.367 0.221 1.00 24.25 6

ATOM 996 O PHE A 127 49.733 15.332 0.490 1.00 23.64 8

ATOM 997 CB PHE A 127 50.454 16.851 -2.264 1.00 25.66 6

ATOM 998 CG PHE A 127 49.518 17.250 -3.398 1.00 24.51 6

ATOM 999 CDl PHE A 127 49.899 18.239 -4.302 1.00 25.76 6

ATOM 1000 CD2 PHE A 127 48.239 16.734 -3.509 1.00 26.77 6

ATOM 1001 CEl PHE A 127 49.026 18.618 -5.301 1.00 27.57 6

ATOM 1002 CE2 PHE A 127 47.381 17.086 -4.518 1.00 27.77 6

ATOM 1003 CZ PHE A 127 47.749 18.072 -5.444 1.00 28.09 6

ATOM 1004 N ARG A 128 51.218 16.966 1.006 1.00 24.68 7

ATOM 1005 CA ARG A 128 51.645 16.377 2.261 1.00 23.44 6

ATOM 1006 C ARG A 128 50.408 16.283 3.155 1.00 21.06 6

ATOM 1007 O ARG A 128 50.190 15.299 3.852 1.00 22.12 8

ATOM 1008 CB ARG A 128 52.743 17.172 2.975 1.00 26.43 6

ATOM 1009 CG ARG A 128 53.051 16.644 4.371 1.00 28.47 6

ATOM 1010 CD ARG A 128 54.116 17.508 5.117 1.00 27.86 6

ATOM 1011 NE ARG A 128 55.345 17.336 4.336 1.00 31.98 7

ATOM 1012 CZ ARG A 128 56.526 17.872 4.699 1.00 36.93 6

ATOM 1013 NHl ARG A 128 56.631 18.561 5.825 1.00 34.28 7

ATOM 1014 NH2 ARG A 128 57.586 17.630 3.912 1.00 38.42 7

ATOM 1015 N GLY A 129 49.588 17.337 3.161 1.00 21.21 7

ATOM 1016 CA GLY A 129 48.391 17.274 4.018 1.00 21.01 6 r--

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ATOM 1091 0 ASN A 139 43.006 2.188 11.154 1.00 20.77 8

ATOM 1092 CB ASN A 139 45.584 3.896 10.226 1.00 18.65 6

ATOM 1093 CG ASN A 139 46.893 3.695 9.486 1.00 21.58 6

ATOM 1094 ODl ASN A 139 47.077 2.678 8.835 1.00 23.27 8

ATOM 1095 ND2 ASN A 139 47.838 4.616 9.605 1.00 23.11 7

ATOM 1096 N LEU A 140 42.380 4.245 10.477 1.00 18.73 7

ATOM 1097 CA LEU A 140 41.227 4.287 11.337 1.00 19.89 6

ATOM 1098 C LEU A 140 40.035 3.500 10.798 1.00 22.66 6

ATOM 1099 O LEU A 140 39.348 2.886 11.581 1.00 23.40 8

ATOM 1100 CB LEU A 140 40.725 5.736 11.530 1.00 19.74 6

ATOM 1101 CG LEU A 140 41.667 6.734 12.211 1.00 20.69 6

ATOM 1102 CDl LEU A 140 41.159 8.189 12.222 1.00 20.47 6

ATOM 1103 CD2 LEU A 140 41.923 6.357 13.687 1.00 21.82 6

ATOM 1104 N VAL A 141 39.777 3.644 9.493 1.00 21.89 7

ATOM 1105 CA VAL A 141 38.625 2.951 8.912 1.00 18.58 6

ATOM 1106 C VAL A 141 38.930 1.566 8.477 1.00 18.27 6

ATOM 1107 O VAL A 141 37.992 0.726 8.348 1.00 21.83 8

ATOM 1108 CB VAL A 141 38.121 3.897 7.749 1.00 17.89 6

ATOM 1109 CGI VAL A 141 37.004 3.204 6.948 1.00 19.45 6

ATOM 1110 CG2 VAL A 141 37.684 5.229 8.360 1.00 19.31 6

ATOM llll N GLN A 142 40.157 1.207 8.147 1.00 19.32 7

ATOM 1112 CA GLN A 142 40.614 -0.046 7.611 1.00 22.31 6

ATOM 1113 C GLN A 142 39.731 -0.535 6.460 1.00 19.60 6

ATOM 1114 O GLN A 142 39.182 -1.647 6.518 1.00 20.68 8

ATOM 1115 CB GLN A 142 40.661 -1.162 8.674 1.00 23.95 6

ATOM 1116 CG GLN A 142 41.594 -0.685 9.829 1.00 28.73 6

ATOM 1117 CD GLN A 142 41.536 -1.705 10.951 1.00 34.39 6

ATOM 1118 OE1 GLN A 142 42.491 -2.469 11.021 1.00 39.24 8

ATOM 1119 NE2 GLN A 142 40.502 -1.784 11.754 1.00 35.26 7

ATOM 1120 N PRO A 143 39.558 0.297 5.442 1.00 18.88 7

ATOM 1121 CA PRO A 143 38.717 -0.119 4.346 1.00 18.57 6

ATOM 1122 C PRO A 143 39.398 -1.140 3.497 1.00 19.27 6

ATOM 1123 O PRO A 143 40.627 -1.225 3.382 1.00 21.22 8

ATOM 1124 CB PRO A 143 38.538 1.179 3.558 1.00 17.81 6

ATOM 1125 CG PRO A 143 39.829 1.905 3.755 1.00 17.73 6

ATOM 1126 CD PRO A 143 40.201 1.627 5.230 1.00 17.54 6

ATOM 1127 N ASP A 144 38.648 -1.982 2.768 1.00 17.55 7

ATOM 1128 CA ASP A 144 39.097 -2.852 1.720 1.00 20.28 6

ATOM 1129 C ASP A 144 39.283 -2.125 0.399 1.00 19.25 6

ATOM 1130 O ASP A 144 40.083 -2.459 -0.481 1.00 20.98 8

ATOM 1131 CB ASP A 144 38.033 -3.936 1.546 1.00 20.76 6

ATOM 1132 CG ASP A 144 37.957 -4.815 2.798 1.00 26.72 6

ATOM 1133 ODl ASP A 144 36.961 -4.629 3.528 1.00 28.28 8

ATOM 1134 OD2 ASP A 144 38.895 -5.587 3.031 1.00 31.50 8

ATOM 1135 N ILE A 145 38.477 -1.081 0.131 1.00 17.25 7

ATOM 1136 CA ILE A 145 38.375 -0.260 -1.035 1.00 18.60 6

ATOM 1137 C ILE A 145 38.239 1.190 -0.687 1.00 18.09 6

ATOM 1138 O ILE A 145 37.607 1.491 0.327 1.00 18.47 8

ATOM 1139 CB ILE A 145 37.081 -0.719 -1.802 1.00 22.13 6

ATOM 1140 CGI ILE A 145 37.350 -2.164 -2.291 1.00 26.63 6

ATOM 1141 CG2 ILE A 145 36.613 0.193 -2.934 1.00 28.58 6

ATOM 1142 CDl ILE A 145 35.987 -2.820 -2.537 1.00 33.01 6

ATOM 1143 N ALA A 146 38.745 2.119 -1.471 1.00 18.54 7

ATOM 1144 CA ALA A 146 38.555 3.525 -1.287 1.00 17.65 6

ATOM 1145 C ALA A 146 38.386 4.174 -2.669 1.00 18.82 6

ATOM 1146 O ALA A 146 39.158 3.831 -3.590 1.00 20.86 8

ATOM 1147 CB ALA A 146 39.754 4.169 -0.561 1.00 17.02 6

ATOM 1148 N CYS A 147 37.421 5.032 -2.758 1.00 17.39 7

ATOM 1149 CA CYS A 147 37.059 5.669 -4.042 1.00 19.79 6

ATOM 1150 C CYS A 147 37.462 7.132 -4.108 1.00 20.20 6

ATOM 1151 O CYS A 147 37.292 7.934 -3.181 1.00 20.69 8

ATOM 1152 CB CYS A 147 35.534 5.576 -4.235 1.00 21.84 6

ATOM 1153 SG CYS A 147 34.881 3.895 -4.275 1.00 25.91 16

ATOM 1154 N PHE A 148 38.073 7.481 -5.256 1.00 20.78 7

ATOM 1155 CA PHE A 148 38.521 8.824 -5.534 1.00 20.56 6

ATOM 1156 C PHE A 148 38.105 9.201 -6.955 1.00 20.31 6

ATOM 1157 O PHE A 148 38.047 8.291 -7.790 1.00 21.33 8

ATOM 1158 CB PHE A 148 40.044 8.856 -5.392 1.00 19.98 6

ATOM 1159 CG PHE A 148 40.527 8.697 -3.964 1.00 21.76 6

ATOM 1160 CDl PHE A 148 40.803 7.418 -3.472 1.00 21.62 6

ATOM 1161 CD2 PHE A 148 40.682 9.781 -3.137 1.00 24.08 6

ATOM 1162 CEl PHE A 148 41.217 7.237 -2.164 1.00 21.64 6

ATOM 1163 CE2 PHE A 148 41.150 9.580 -1.833 1.00 22.23 6

ATOM 1164 CZ PHE A 148 41.384 8.321 -1.337 1.00 21.48 6 ATOM 1165 NN GLY A 149 37.874 10,.485 -7..215 1.00 19.66

ATOM 1166 C CAA GLY A 149 37.457 10. .782 -8, .630 1. 00 19. 28

ATOM 1167 C C GLY A 149 38.663 10. .981 -9. .537 1. 00 21. 16

ATOM 1168 O O GLY A 149 39.696 11. .548 -9. .117 1. 00 25. 03

ATOM 1169 N N GLU A 150 38.524 10, .707 -10, .848 1. 00 21. 70

ATOM 1170 C CAA GLU A 150 39.588 10, .939 -11, .809 1. 00 25. 98

ATOM 1171 C C GLU A 150 39.777 12 .386 -12, .160 1. 00 25. 10

ATOM 1172 O O GLU A 150 40.841 12, .764 -12. .668 1. 00 26. 55

ATOM 1173 C CBB GLU A 150 39.316 10, .178 -13. .146 1. 00 28. 34

ATOM 1174 C CGG GLU A 150 39.447 8.683 -12.924 1. 00 30. 38

ATOM 1175 C CDD GLU A 150 39.464 7.923 -14.241 1. 00 36. 75

ATOM 1176 OE1 GLU A 150 39.222 8.536 -15.309 1. 00 39. 43

ATOM 1177 OE2 GLU A 150 39.770 6.715 -14.171 1. 00 39. 37

ATOM 1178 N N LYS A 151 38.795 13.240 -11.874 1. 00 25. 17 7

ATOM 1179 C CAA LYS A 151 38.970 14.660 -12.162 1. 00 28. 17 6

ATOM 1180 C C LYS A 151 40.159 15.229 -11.400 1. 00 29. 47 6

ATOM 1181 O O LYS A 151 40.955 16.017 -11 .930 1. .00 29. 69 8

ATOM 1182 C CBB LYS A 151 37.710 15.423 11.787 1 1.. .00 30. 49 6

ATOM 1183 C CGG LYS A 151 37.865 16.877 12.255 1 1.. .00 34. .63 6

ATOM 1184 C CDD LYS A 1 15511 37.021 17.827 11.434 1 1.. ,00 40. 81 6

ATOM 1185 C CEE LYS A 115511 37.161 19.249 12.007 1 1.. .00 42. 71 6

ATOM 1186 N NZZ LYS A 151 35.905 20.032 11.825 1 1.. .00 46. 87 7

ATOM 1187 N N ASP A 152 40.274 14.877 10.114 1 1.. .00 26. 84 7

ATOM 1188 C CAA ASP A 152 41.456 15.268 -9.322 1 1., .00 26. ,83 6

ATOM 1189 C C ASP A 152 42.545 14.241 -9.529 1 1., .00 26. ,30 6

ATOM 1190 O O ASP A 152 42.933 13.366 -8.715 1 1.. ,00 24. 28 8

ATOM 1191 C CBB ASP A 152 41.078 15.419 -7.846 1. .00 29. .39 6

ATOM 1192 N N PHE A 153 43.137 14.340 10.746 1. .00 24. 76 7

ATOM 1193 C CAA PHE A 153 44.063 13.342 11.241 1 1.. .00 24. ,28 6

ATOM 1194 C C PHE A 153 45.350 13.353 10.435 1 1. .00 24. .40 6

ATOM 1195 O O PHE A 153 45.891 12.270 -10.274 1 1., .00 24. .91 8

ATOM 1196 C CBB PHE A 153 44.385 13.509 -12.748 1 1., .00 26, .30 6

ATOM 1197 C CGG PHE A 153 45.137 14.809 -12.939 1 1., .00 29. ,67 6

ATOM 1198 CDl PHE A 153 46.517 14.828 -13.025 1, .00 30. .48 6

ATOM 1199 CD2 PHE A 153 44.443 16.015 -13.033 1 .00 32. .69 6

ATOM 1200 CEl PHE A 153 47.203 16.017 13 .147 1 .00 31, .59 6

ATOM 1201 CE2 PHE A 153 45.124 17.212 13 .186 1 .00 33, .09 6

ATOM 1202 CZ PHE A 153 46.511 17.215 13 .241 1 .00 34, .20 6

ATOM 1203 N N GLN A 154 45.781 14.510 -9. .931 1 .00 25, . ,9988 7

ATOM 1204 C CAA GLN A 154 47.028 14.521 -9 .174 1 .00 22. . ,8855 6

ATOM 1205 C C GLN A 154 46.851 13.825 -7 .837 1 .00 22, . ,3388 6

ATOM 1206 O 0 GLN A 154 47.695 13.032 -7 .413 1 1 .,00 22 .53 8

ATOM 1207 C CBB GLN A 154 47.542 15.952 -8 .933 11 ..00 24, .08 6

ATOM 1208 C CGG GLN A 154 48.929 15.967 -8 .287 11 ..00 26 .39 6

ATOM 1209 C CDD GLN A 154 49.688 17.287 -8 .508 11 ..00 28 .37 6

ATOM 1210 OE1 GLN A 154 49.098 18.244 -8 .993 11 ..00 28, .49 8

ATOM 1211 NE2 GLN A 154 50.978 17.318 -8 .158 11 ..00 26 .87 7

ATOM 1212 N N GLN A 155 45.747 14.096 -7 .174 1 .00 21 .22 7

ATOM 1213 C CAA GLN A 155 45.470 13.411 -5 .896 1 .00 21 .76 6

ATOM 1214 C C GLN A 155 45.362 11.902 -6 .092 1 .00 21 .39

ATOM 1215 O O G GLLNN A A 1 1 1555555 45.852 11.100 -5 .289 1 .00 20 .96

ATOM 1216 C CBB G GLLNN A A 1 1 1555555 44.157 13.885 -5 .251 1 .00 23 .33 6

ATOM 1217 CG GLN A 155 44.285 15.020 -4 .241 0 .50 22 .16 6

ATOM 1218 CD GLN A 155 43.185 14.991 -3 .184 0 .50 22 .84 6

ATOM 1219 OE1 GGLLNN A 115555 42.574 13.952 -2 .872 0 .50 25 .23 8

ATOM 1220 NE2 GGLLNN A 115555 42.921 16.140 -2 .600 0 .50 20 .85 7

ATOM 1221 N LEU A 156 44.752 11.455 -7.214 1 .00 20 .25 7

ATOM 1222 CA LEU A 156 44.592 10.045 -7.465 1 .00 18 .93 6

ATOM 1223 C LEU A 156 45.938 9.367 -7.681 1 .00 20 .91 6

ATOM 1224 O LEU A 156 46.240 8.334 -7.081 1 .00 20 .99 8

ATOM 1225 CB LEU A 156 43.684 9.840 -8.695 1 .00 20 .06 6

ATOM 1226 CG LEU A 156 43.409 8.396 -9.060 1 .00 21 .79 6

ATOM 1227 CDl LEU A 156 42.773 7.624 -7.893 1 .00 20 .19 6

ATOM 1228 CD2 LEU A 156 42.493 367 -10.300 1 .00 23 .41 6

ATOM 1229 N ALA A 157 46.790 991 -8.498 1 .00 21 .27 7

ATOM 1230 CA ALA A 157 48.139 9.424 -8.654 1 .00 20 .85 6

ATOM 1231 C ALA A 157 48.896 9.402 -7.339 1 .00 22 .15 6

ATOM 1232 0 ALA A 157 49.617 8.451 -7.039 1 .00 23 .09

ATOM 1233 CB ALA A 157 48.919 10.292 -9.658 1 .00 21 .65

ATOM 1234 N LEU A 158 48.771 10.447 -6.537 1 .00 21 .63

ATOM 1235 CA LEU A 158 49.507 10.508 -5.235 1 .00 20 .79

ATOM 1236 C LEU A 158 49.117 9.373 -4.311 1 .00 22 .51

ATOM 1237 0 LEU A 158 49.950 8.663 -3.702 1 .00 22 .35

ATOM 1238 CB LEU A 158 49.227 11.847 -4.583 1 .00 23 .18 ATOM 1239 CG LEU A 158 49.828 12.175 -3.211 1.00 25.19 6

ATOM 1240 CDl LEU A 158 51.099 12.952 -3.381 1.00 28.19 6

ATOM 1241 CD2 LEU A 158 48.782 12.989 -2.433 1.00 26.28 6

ATOM 1242 N ILE A 159 47.765 9.231 -4.212 1.00 18.01 7

ATOM 1243 CA ILE A 159 47.322 8.127 -3.317 1.00 19.99 6

ATOM 1244 C ILE A 159 47.680 6.760 -3.864 1.00 18.66 6

ATOM 1245 O ILE A 159 48.038 5.871 -3.083 1.00 19.24 8

ATOM 1246 CB ILE A 159 45.805 8.275 -3.083 1.00 23.08 6

ATOM 1247 CGI ILE A 159 45.455 9.626 -2.443 1.00 21.73 6

ATOM 1248 CG2 ILE A 159 45.232 7.181 -2.187 1.00 23.20 6

ATOM 1249 CDl ILE A 159 46.056 9.774 -1.063 1.00 27.28 6

ATOM 1250 N ARG A 160 47.514 6.493 -5.148 1.00 20.78 7

ATOM 1251 CA ARG A 160 47.956 5.202 -5.694 1.00 20.24 6

ATOM 1252 C ARG A 160 49.422 4.914 -5.397 1.00 21.57 6

ATOM 1253 O ARG A 160 49.738 3.802 -4.971 1.00 19.80 8

ATOM 1254 CB ARG A 160 47.708 5.074 -7.218 1.00 21.86 6

ATOM 1255 CG ARG A 160 46.192 5.007 -7.567 1.00 21.60 6

ATOM 1256 CD ARG A 160 46.195 4.575 -9.066 1.00 25.76 6

ATOM 1257 NE ARG A 160 44.867 4.625 -9.678 1.00 29.84 7

ATOM 1258 CZ ARG A 160 43.905 3.713 -9.455 1.00 32.53 6

ATOM 1259 NHl ARG A 160 44.040 2.653 -8.651 1.00 32.58 7

ATOM 1260 NH2 ARG A 160 42.788 3.911 -10.168 1.00 34.80 7

ATOM 1261 N LYS A 161 50.322 5.905 -5.460 1.00 20.74 7

ATOM 1262 CA LYS A 161 51.733 5.714 -5.164 1.00 19.39 6

ATOM 1263 C LYS A 161 51.925 5.506 -3.674 1.00 19.31 6

ATOM 1264 O LYS A 161 52.628 4.596 -3.191 1.00 22.15 8

ATOM 1265 CB LYS A 161 52.523 6.929 -5.649 1.00 21.10 6

ATOM 1266 CG LYS A 161 54.009 6.900 -5.202 1.00 24.79 6

ATOM 1267 CD LYS A 161 54.612 5.615 -5.820 1.00 28.31 6

ATOM 1268 CE LYS A 161 56.100 5.758 -6.162 1.00 31.56 6

ATOM 1269 NZ LYS A 161 56.913 6.424 -5.128 1.00 26.44 7

ATOM 1270 N MET A 162 51.191 6.312 -2.834 1.00 20.30 7

ATOM 1271 CA MET A 162 51.287 6.115 -1.383 1.00 18.85 6

ATOM 1272 C MET A 162 50.851 4.750 -0.908 1.00 21.35 6

ATOM 1273 O MET A 162 51.504 4.085 -0.089 1.00 20.93 8

ATOM 1274 CB MET A 162 50.412 7.231 -0.702 1.00 21.14 6

ATOM 1275 CG MET A 162 50.512 7.132 0.818 1.00 21.47 6

ATOM 1276 SD MET A 162 49.291 8.186 1.642 1.00 23.59 16

ATOM 1277 CE MET A 162 47.948 6.994 1.780 1.00 27.52 6

ATOM 1278 N VAL A 163 49.808 4.217 -1.577 1.00 19.66 7

ATOM 1279 CA VAL A 163 49.304 2.897 -1.214 1.00 20.50 6

ATOM 1280 C VAL A 163 50.289 1.806 -1.612 1.00 19.37 6

ATOM 1281 O VAL A 163 50.554 0.867 -0.837 1.00 20.07 8

ATOM 1282 CB VAL A 163 47.914 2.672 -1.873 1.00 21.79 6

ATOM 1283 CGI VAL A 163 47.540 1.204 -1.894 1.00 22.15 6

ATOM 1284 CG2 VAL A 163 46.897 3.536 -1.100 1.00 22.77 6

ATOM 1285 N ALA A 164 50.784 1.931 -2.837 1.00 21.03 7

ATOM 1286 CA ALA A 164 51.773 0.937 -3.276 1.00 22.98 6

ATOM 1287 C ALA A 164 53.006 0.925 -2.380 1.00 23.44 6

ATOM 1288 O ALA A 164 53.478 -0.126 -1.927 1.00 23.96 8

ATOM 1289 CB ALA A 164 52.136 1.263 -4.719 1.00 23.95 6

ATOM 1290 N ASP A 165 53.552 2.121 -2.154 1.00 21.54 7

ATOM 1291 CA ASP A 165 54.788 2.231 -1.387 1.00 23.74 6

ATOM 1292 C ASP A 165 54.639 1.784 0.052 1.00 24.26 6

ATOM 1293 O ASP A 165 55.440 1.000 0.544 1.00 24.84 8

ATOM 1294 CB ASP A 165 55.321 3.664 -1.384 1.00 22.61 6

ATOM 1295 CG ASP A 165 55.980 4.130 -2.662 1.00 24.69 6

ATOM 1296 ODl ASP A 165 56.269 3.286 -3.531 1.00 24.19 8

ATOM 1297 OD2 ASP A 165 56.220 5.356 -2.781 1.00 24.88 8

ATOM 1298 N MET A 166 53.590 2.288 0.725 1.00 21.43 7

ATOM 1299 CA MET A 166 53.378 2.007 2.157 1.00 20.10 6

ATOM 1300 C MET A 166 52.785 0.652 2.486 1.00 21.04 6

ATOM 1301 O MET A 166 52.605 0.347 3.671 1.00 21.28 8

ATOM 1302 CB MET A 166 52.540 3.142 2.751 1.00 20.75 6

ATOM 1303 CG MET A 166 53.288 4.458 2.868 1.00 22.14 6

ATOM 1304 SD MET A 166 55.034 4.259 3.242 1.00 26.84 16

ATOM 1305 CE MET A 166 54.959 3.835 4.983 1.00 27.47 6

ATOM 1306 N GLY A 167 52.458 -0.170 1.510 1.00 20.03 7

ATOM 1307 CA GLY A 167 51.975 -1.522 1.790 1.00 22.00 6

ATOM 1308 C GLY A 167 50.526 -1.606 2.218 1.00 20.49 6

ATOM 1309 O GLY A 167 50.190 -2.660 2.782 1.00 24.46 8

ATOM 1310 N PHE A 168 49.685 -0.585 2.002 1.00 21.54 7

ATOM 1311 CA PHE A 168 48.287 -0.824 2.403 1.00 20.47 6

ATOM 1312 C PHE A 168 47.645 -1.917 1.546 1.00 19.05 6 ATOM 1313 O PHE A 168 47.704 -1.739 0.320 1.00 20.71 8

ATOM 1314 CB PHE A 168 47.563 0.509 2.296 1.00 21.24 6

ATOM 1315 CG PHE A 168 47.788 1.632 3.277 1.00 20.78 6

ATOM 1316 CDl PHE A 168 48.548 2.751 2.932 1.00 22.23 6

ATOM 1317 CD2 PHE A 168 47.186 1.509 4.509 1.00 21.78 6

ATOM 1318 CEl PHE A 168 48.736 3.747 3.913 1.00 20.66 6

ATOM 1319 CE2 PHE A 168 47.353 2.544 5.432 1.00 19.66 6

ATOM 1320 CZ PHE A 168 48.085 3.665 5.136 1.00 20.15 6

ATOM 1321 N ASP A 169 46.769 -2.693 2.126 1.00 22.42 7

ATOM 1322 CA ASP A 169 46.084 -3.767 1.356 1.00 22.89 6

ATOM 1323 C ASP A 169 44.743 -3.167 0.938 1.00 23.53 6

ATOM 1324 O ASP A 169 43.705 -3.617 1.427 1.00 23.13 8

ATOM 1325 CB ASP A 169 45.975 -5.057 2.147 1.00 28.05 6

ATOM 1326 CG ASP A 169 45.399 -6.229 1.376 1.00 32.61 6

ATOM 1327 ODl ASP A 169 45.492 -6.192 0.129 1.00 35.09 8

ATOM 1328 OD2 ASP A 169 44.838 -7.159 1.975 1.00 37.69 8

ATOM 1329 N ILE A 170 44.751 -2.104 0.146 1.00 21.02 7

ATOM 1330 CA ILE A 170 43.499 -1.409 -0.181 1.00 21.69 6

ATOM 1331 C ILE A 170 43.372 -1.265 -1.677 1.00 21.49 6

ATOM 1332 O ILE A 170 44.334 -0.773 -2.304 1.00 22.63 8

ATOM 1333 CB ILE A 170 43.443 -0.013 0.493 1.00 21.71 6

ATOM 1334 CGI ILE A 170 43.459 -0.124 2.030 1.00 21.39 6

ATOM 1335 CG2 ILE A 170 42.221 0.770 0.037 1.00 22.28 6

ATOM 1336 CDl ILE A 170 43.745 1.240 2.694 1.00 23.40 6

ATOM 1337 N GLU A 171 42.206 -1.583 -2.244 1.00 22.35 7

ATOM 1338 CA GLU A 171 41.960 -1.346 -3.656 1.00 22.51 6

ATOM 1339 C GLU A 171 41.609 0.133 -3.871 1.00 22.05 6

ATOM 1340 O GLU A 171 40.625 O.577 -3.278 1.00 20.97 8

ATOM 1341 CB GLU A 171 40.841 -2.288 -4.152 1.00 21.82 6

ATOM 1342 CG GLU A 171 40.514 -1.978 -5.601 1.00 28.71 6

ATOM 1343 CD GLU A 171 39.364 -2.857 -6.098 1.00 34.21 6

ATOM 1344 OE1 GLU A 171 38.911 -3.740 -5.361 1.00 36.00 8

ATOM 1345 OE2 GLU A 171 38.953 -2.650 -7.272 1.00 38.31 8

ATOM 1346 N ILE A 172 42.352 0.886 -4.680 1.00 20.37 7

ATOM 1347 CA ILE A 172 42.017 2.294 -4.940 1.00 19.10 6

ATOM 1348 C ILE A 172 41.196 2.347 -6.217 1.00 23.26 6

ATOM 1349 O ILE A 172 41.716 1.875 -7.239 1.00 26.08 8

ATOM 1350 CB ILE A 172 43.306 3.159 -5.019 1.00 22.26 6

ATOM 1351 CGI ILE A 172 44.060 2.969 -3.686 1.00 21.42 6

ATOM 1352 CG2 ILE A 172 42.975 4.587 -5.345 1.00 23.49 6

ATOM 1353 CDl ILE A 172 43.283 3.498 -2.483 1.00 22.09 6

ATOM 1354 N VAL A 173 39.937 2.751 -6.114 1.00 20.87 7

ATOM 1355 CA VAL A 173 39.045 2.789 -7.278 1.00 23.09 6

ATOM 1356 C VAL A 173 39.073 4.218 -7.811 1.00 23.54 6

ATOM 1357 O VAL A 173 38.637 5.125 -7.058 1.00 23.05 8

ATOM 1358 CB VAL A 173 37.637 2.318 -6.861 1.00 22.84 6

ATOM 1359 CGI VAL A 173 36.675 2.449 -8.040 1.00 24.23 6

ATOM 1360 CG2 VAL A 173 37.756 0.893 -6.307 1.00 23.19 6

ATOM 1361 N GLY A 174 39.480 4.451 -9.055 1.00 22.79 7

ATOM 1362 CA GLY A 174 39.509 5.765 -9.652 1.00 22.28 6

ATOM 1363 C GLY A 174 38.217 5.872 -10.462 1.00 25.76 6

ATOM 1364 O GLY A 174 37.972 4.984 -11.306 1.00 25.34 8

ATOM 1365 N VAL A 175 37.340 6.803 -10.087 1.00 22.69 7

ATOM 1366 CA VAL A 175 35.996 6.810 -10.712 1.00 21.96 6

ATOM 1367 C VAL A 175 36.025 7.779 -11.858 1.00 22.74 6

ATOM 1368 O VAL A 175 36.298 8.938 -11.632 1.00 19.20 8

ATOM 1369 CB VAL A 175 34.977 7.161 -9.632 1.00 21.95 6

ATOM 1370 CGI VAL A 175 33.557 7.328 -10.233 1.00 23.84 6

ATOM 1371 CG2 VAL A 175 34.914 6.111 -8.501 1.00 20.67 6

ATOM 1372 N PRO A 176 35.590 7.430 -13.068 1.00 23.97 7

ATOM 1373 CA PRO A 176 35.714 8.344 -14.172 1.00 26.00 6

ATOM 1374 C PRO A 176 34.750 9.485 -14.090 1.00 23.25 6

ATOM 1375 O PRO A 176 33.689 9.357 -13.462 1.00 23.13 8

ATOM 1376 CB PRO A 176 35.429 7.464 -15.401 1.00 26.90 6

ATOM 1377 CG PRO A 176 35.554 6.062 -14.946 1.00 30.42 6

ATOM 1378 CD PRO A 176 35.214 6.053 -13.467 1.00 26.21 6

ATOM 1379 N ILE A 177 35.026 10.601 -14.706 1.00 25.15 7

ATOM 1380 CA ILE A 177 34.220 11.792 -14.882 1.00 25.60 6

ATOM 1381 C ILE A 177 32.858 11.452 -15.470 1.00 26.15 6

ATOM 1382 O ILE A 177 32.823 10.610 -16.392 1.00 25.13 8

ATOM 1383 CB ILE A 177 35.002 12.755 -15.816 1.00 27.16 6

ATOM 1384 CGI ILE A 177 36.095 13.432 -14.910 1.00 32.12 6

ATOM 1385 CG2 ILE A 177 34.203 13.794 -16.565 1.00 27.48 6

ATOM 1386 CDl ILE A 177 37.253 13.907 -15.774 1.00 33.86 6 ATOM 1387 N MET A 178 31.789 11.892 -14.839 1.00 23.56 7

ATOM. 1388 CA MET A 178 30.439 11.695 -15.338 1.00 22.41 6

ATOM 1389 C MET A 178 30.253 12.624 -16.564 1.00 19.13 6

ATOM 1390 O MET A 178 30.623 13.780 -16.493 1.00 19.54 8

ATOM 1391 CB MET A 178 29.352 12.079 -14.359 1.00 28.06 6

ATOM 1392 CG MET .A 178 29.443 11.331 -13.018 1.00 34.50 6

ATOM 1393 SD MET A 178 28.135 11.774 -11.868 1.00 41.82 16

ATOM 1394 CE MET A 178 28.027 13.573 -11.994 1.00 44.07 6

ATOM 1395 N ARG A 179 29.559 12.130 -17.573 1.00 19.57 7

ATOM 1396 CA ARG A 179 29.384 12.934 -18.776 1.00 18.81 6

ATOM 1397 C ARG A 179 27.950 12.914 -19.257 1.00 19.43 6

ATOM 1398 O ARG A 179 27.182 12.014 -18.938 1.00 19.78 8

ATOM 1399 CB ARG A 179 30.252 12.380 -19.936 1.00 20.44 6

ATOM 1400 CG ARG A 179 31.757 12.403 -19.680 1.00 21.94 6

ATOM 1401 CD ARG A 179 32.547 11.665 -20.791 1.00 22.96 6

ATOM 1402 NE ARG A 179 33.928 11.849 -20.377 1.00 24.17 7

ATOM 1403 CZ ARG A 179 34.636 12.995 -20.379 1.00 23.08 6

ATOM 1404 NHl ARG A 179 34.146 14.147 -20.883 1.00 22.58 7

ATOM 1405 NH2 ARG A 179 35.872 12.925 -19.895 1.00 25.87 7

ATOM 1406 N ALA A 180 27.526 13.954 -19.931 1.00 19.29 7

ATOM 1407 CA ALA A 180 26.247 14.023 -20.609 1.00 20.57 6

ATOM 1408 C ALA A 180 26.269 13.017 -21.785 1.00 20.46 6

ATOM 1409 O ALA A 180 27.305 12.438 -22.089 1.00 20.53 8

ATOM 1410 CB ALA A 180 26.009 15.430 -21.100 1.00 20.95 6

ATOM 1411 N LYS A 181 25.065 12.823 -22.355 1.00 23.00 7

ATOM 1412 CA LYS A 181 24.978 11.807 -23.436 1.00 25.24 6

ATOM 1413 C LYS A 181 25.745 12.150 -24.672 1.00 23.73 6

ATOM 1414 O LYS A 181 26.108 11.238 -25.439 1.00 25.08 8

ATOM 1415 CB LYS A 181 23.496 11.637 -23.802 1.00 25.36 6

ATOM 1416 CG LYS A 181 22.670 10.939 -22.755 1.00 29.60 6

ATOM 1417 CD LYS A 181 23.217 9.642 -22.291 1.00 31.75 6

ATOM 1418 N ASP A 182 26.027 13.427 -24.854 1.00 22.41 7

ATOM 1419 CA ASP A 182 26.844 13.896 -25.958 1.00 23.30 6

ATOM 1420 C ASP A 182 28.319 13.944 -25.618 1.00 24.01 6

ATOM 1421 O ASP A 182 29.102 14.328 -26.481 1.00 23.06 8

ATOM 1422 CB ASP A 182 26.269 15.241 -26.435 1.00 23.96 6

ATOM 1423 CG ASP A 182 26.307 16.365 -25.427 1.00 25.62 6

ATOM 1424 ODl ASP A 182 26.954 16.241 -24.359 1.00 24.83 8

ATOM 1425 OD2 ASP A 182 25.690 17.397 -25.755 1.00 27.42 8

ATOM 1426 N GLY A 183 28.808 13.557 -24.413 1.00 19.95 7

ATOM 1427 CA GLY A 183 30.201 13.464 -24.071 1.00 23.13 6

ATOM 1428 C GLY A 183 30.666 14.607 -23.127 1.00 19.95 6

ATOM 1429 O GLY A 183 31.799 14.532 -22.661 1.00 21.39 8

ATOM 1430 N LEU A 184 29.882 15.681 -23.119 1.00 19.14 7

ATOM 1431 CA LEU A 184 30.339 16.847 -22.301 1.00 18.16 6

ATOM 1432 C LEU A 184 30.494 16.470 -20.832 1.00 18.40 6

ATOM 1433 O LEU A 184 29.587 15.913 -20.225 1.00 19.97 8

ATOM 1434 CB LEU A 184 29.377 18.028 -22.486 1.00 18.63 6

ATOM 1435 CG LEU A 184 29.738 19.280 -21.652 1.00 17.34 6

ATOM 1436 CDl LEU A 184 31.065 19.909 -22.111 1.00 19.12 6

ATOM 1437 CD2 LEU A 184 28.615 20.311 -21.740 1.00 19.88 6

ATOM 1438 N ALA A 185 31.607 16.870 -20.184 1.00 16.12 7

ATOM 1439 CA ALA A 185 31.782 16.555 -18.761 1.00 18.63 6

ATOM 1440 C ALA A 185 30.744 17.337 -17.942 1.00 17.79 6

ATOM 1441 O ALA A 185 30.537 18.511 -18.196 1.00 18.57 8

ATOM 1442 CB ALA A 185 33.237 16.872 -18.396 1.00 20.34 6

ATOM 1443 N LEU A 186 30.024 16.634 -17.065 1.00 16.87 7

ATOM 1444 CA LEU A 186 29.020 17.352 -16.271 1.00 16.99 6

ATOM 1445 C LEU A 186 29.790 18.284 -15.327 1.00 17.67 6

ATOM 1446 O LEU A 186 30.768 17.866 -14.658 1.00 20.34 8

ATOM 1447 CB LEU A 186 28.117 16.384 -15.513 1.00 16.87 6

ATOM 1448 CG LEU A 186 27.300 15.408 -16.358 1.00 18.67 6

ATOM 1449 CDl LEU A 186 26.353 14.626 -15.456 1.00 20.67 6

ATOM 1450 CD2 LEU A 186 26.520 16.166 -17.415 1.00 17.31 6

ATOM 1451 N SER A 187 29.252 19.481 -15.220 1.00 18.83 7

ATOM 1452 CA SER A 187 29.915 20.486 -14.382 1.00 17.18 6

ATOM 1453 C SER A 187 29.000 21.631 -14.105 1.00 17.64 6

ATOM 1454 O SER A 187 28.216 22.057 -14.964 1.00 18.63 8

ATOM 1455 CB SER A 187 31.153 21.021 -15.151 1..00 20.23 6

ATOM 1456 OG SER A 187 31.730 22.134 -14.430 1.00 20.91 8

ATOM 1457 N SER A 188 29.176 22.275 -12.905 1.00 17.55 7

ATOM 1458 CA SER A 188 28.463 23.548 -12.722 1.00 17.70 6

ATOM 1459 C SER A 188 28.806 24.605 -13.755 1.00 17.74 6

ATOM 1460 O SER A 188 28.014 25.522 -14.095 1.00 18.92 8 -J n CT) 01 cπ -fe. O co NJ N3 o cπ o Cn O Cπ O cπ 0 Cπ σ cπ O Cπ

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ATOM 1531 0 ARG A 198 26.761 22.214 -26.214 1.00 25.17 8 ATOM 1532 CB ARG A 198 24.831 24.133 -24.454 1.00 22.16 6 ATOM 1533 CG ARG A 198 24.576 22.689 -23.946 1.00 21.81 6 ATOM 1534 CD ARG A 198 25.656 22.194 -23.010 1.00 22.56 6 ATOM 1535 NE ARG A 198 25.386 20.830 -22.532 1.00 21.88 7 ATOM 1536 CZ ARG A 198 25.614 19.724 -23.247 1.00 24.32 6 ATOM 1537 NHl ARG A 198 25.384 18.481 -22.824 1.00 23.45 7 ATOM 1538 NH2 ARG A 198 26.118 19.830 -24.477 1.00 25.14 7 ATOM 1539 N LYS A 199 25.707 23.649 -27.549 1.00 23.80 7 ATOM 1540 CA LYS A 199 25.820 22.710 -28.684 1.00 22.66 6 ATOM 1541 C LYS A 199 27.221 22.558 -29.202 1.00 22.59 6 ATOM 1542 0 LYS A 199 27.608 21.508 -29.753 1.00 24.00 8 ATOM 1543 CB LYS A 199 24.855 23.272 -29.743 1.00 25.23 6 ATOM 1544 CG LYS A 199 24.661 22.284 -30.903 1.00 27.40 6 ATOM 1545 CD LYS A 199 23.602 22.991 -31.802 1.00 32.35 6

ATOM 1546 CE LYS A 199 23.336 22.059 -32.983 1.00 36.02 6

ATOM 1547 NZ LYS A 199 22.311 22.674 -33.894 1.00 38.59 7

ATOM 1548 N ILE A 200 28.111 23.556 -29.074 1.00 22.04 7

ATOM 1549 CA ILE A 200 29.513 23.458 -29.440 1.00 25.05 6

ATOM 1550 C ILE A 200 30.415 22.725 -28.438 1.00 23.70 6

ATOM 1551 O ILE A 200 31.347 21.980 -28.775 1.00 22.15 8

ATOM 1552 CB ILE A 200 30.128 24.863 -29.575 1.00 25.43 6

ATOM 1553 CGI ILE A 200 29.457 25.528 -30.809 1.00 26.99 6

ATOM 1554 CG2 ILE A 200 31.644 24.911 -29.704 1.00 26.61 6

ATOM 1555 CDl ILE A 200 29.746 27.029 -30.827 1.00 28.65 6

ATOM 1556 N ALA A 201 29.987 22.836 -27.170 1.00 22.88 7

ATOM 1557 CA ALA A 201 30.773 22.278 -26.053 1.00 24.80 6

ATOM 1558 C ALA A 201 31.217 20.829 -26.110 1.00 23.52 6

ATOM 1559 O ALA A 201 32.363 20.607 -25.709 1.00 21.96 8

ATOM 1560 CB ALA A 201 29.913 22.499 -24.781 1.00 24.70 6

ATOM 1561 N PRO A 202 30.498 19.846 -26.659 1.00 24.18 7

ATOM 1562 CA PRO A 202 30.946 18.473 -26.796 1.00 24.19 6

ATOM 1563 C PRO A 202 32.191 18.288 -27.649 1.00 26.04 6

ATOM 1564 O PRO A 202 32.900 17.282 -27.556 1.00 25.77 8

ATOM 1565 CB PRO A 202 29.759 17.693 -27.382 1.00 24.31 6

ATOM 1566 CG PRO A 202 28.579 18.572 -27.068 1.00 23.02 6

ATOM 1567 CD PRO A 202 29.073 19.991 -27.051 1.00 22.33 6

ATOM 1568 N GLY A 203 32.559 19.351 -28.406 1.00 25.61 7

ATOM 1569 CA GLY A 203 33.779 19.327 -29.179 1.00 26.22 6

ATOM 1570 C GLY A 203 35.012 19.196 -28.324 1.00 24.81 6

ATOM 1571 O GLY A 203 36.061 18.750 -28.817 1.00 24.88 8

ATOM 1572 N LEU A 204 34.999 19.724 -27.082 1.00 23.90 7

ATOM 1573 CA LEU A 204 36.199 19.561 -26.254 1.00 23.72 6

ATOM 1574 C LEU A 204 36.550 18.119 -26.035 1.00 23.32 6

ATOM 1575 O LEU A 204 37.689 17.689 -26.239 1.00 24.33 8

ATOM 1576 CB LEU A 204 35.957 20.361 -24.936 1.00 24.53 6

ATOM 1577 CG LEU A 204 37.111 20.290 -23.972 1.00 25.84 6

ATOM 1578 CDl LEU A 204 38.425 20.791 -24.586 1.00 26.75 6

ATOM 1579 CD2 LEU A 204 36.806 21.156 -22.742 1.00 26.68 6

ATOM 1580 N TYR A 205 35.580 17.243 -25.663 1.00 21.57 7

ATOM 1581 CA TYR A 205 35.804 15.836 -25.435 1.00 22.36 6

ATOM 1582 C TYR A 205 36.200 15.116 -26.748 1.00 21.69 6

ATOM 1583 O TYR A 205 37.041 14.212 -26.762 1.00 23.95 8

ATOM 1584 CB TYR A 205 34.533 15.211 -24.809 1.00 21.96 6

ATOM 1585 CG TYR A 205 34.766 13.758 -24.505 1.00 25.55 6

ATOM 1586 CDl TYR A 205 35.727 13.322 -23.619 1.00 27.86 6

ATOM 1587 CD2 TYR A 205 34.059 12.802 -25.253 1.00 29.16 6

ATOM 1588 CEl TYR A 205 35.901 11.979 -23.364 1.00 30.07 6

ATOM 1589 CE2 TYR A 205 34.261 11.448 -25.003 1.00 30.89 6

ATOM 1590 CZ TYR A 205 35.158 11.053 -24.064 1.00 32.67 6

ATOM 1591 OH TYR A 205 35.373 9.702 -23.839 1.00 36.20 8

ATOM 1592 N LYS A 206 35.652 15.679 -27.833 1.00 23.35 7

ATOM 1593 CA LYS A 206 36.040 15.114 -29.149 1.00 24.75 6

ATOM 1594 C LYS A 206 37.530 15.306 -29.401 1.00 24.74 6

ATOM 1595 O LYS A 206 38.252 14.359 -29.757 1.00 26.16 8

ATOM 1596 CB LYS A 206 35.223 15.740 -30.293 1.00 25.21 6

ATOM 1597 CG LYS A 206 33.784 15.236 -30.295 1.00 30.61 6

ATOM 1598 CD LYS A 206 33.118 15.648 -31.621 1.00 34.58 6

ATOM 1599 CE LYS A 206 31.600 15.547 -31.489 1.00 37.70 6

ATOM 1600 NZ LYS A 206 30.951 15.934 -32.794 1.00 40.74 7

ATOM 1601 N VAL A 207 37.995 16.518 -29.128 1.00 25.56 7

ATOM 1602 CA VAL A 207 39.432 16.818 -29.324 1.00 26.41 6

ATOM 1603 C VAL A 207 40.240 16.016 -28.333 1.00 26.75 6

ATOM 1604 O VAL A 207 41.246 15.351 -28.662 1.00 26.06 8 ATOM 1605 CB VAL A 207 39.714 18.318 -29.266 1.00 26.88 6

ATOM 1606 CGI VAL A 207 41. 212 18.590 -29. 172 1. 00 27. 69 6

ATOM 1607 CG2 VAL A 207 39. 062 18.967 -30. 489 1. 00 27. 15 6

ATOM 1608 N LEU A 208 39. 793 15.917 -27. 065 1. 00 26. 81 7

ATOM 1609 CA LEU A 208 40. 472 15.110 -26. 079 1. 00 26. 80 6

ATOM 1610 C LEU A 208 40. 555 13.645 -26. 462 1. 00 27. 53 6

ATOM 1611 O LEU A 208 41. 616 13.017 -26. 276 1. 00 27. 79 8

ATOM 1612 CB LEU A 208 39. 736 15.325 -24. 732 1. 00 28. 31 6

ATOM 1613 CG LEU A 208 40. 248 14.531 -23. 535 1. 00 31. 14 6

ATOM 1614 CDl LEU A 208 41. 649 14.906 -23. 142 1. 00 31. 37 6

ATOM 1615 CD2 LEU A 208 39. 288 14.741 -22. 347 1. 00 33. 29 6

ATOM 1616 N SER A 209 39. 539 13.042 -27. 028 1. 00 26. 96 7

ATOM 1617 CA SER A 209 39. 536 11.655 -27. 442 1. 00 28. 65 6

ATOM 1618 C SER A 209 40. 427 11.463 -28. 696 1. 00 30. 30 6

ATOM 1619 O SER A 209 41. 021 10.401 -28. 829 1. 00 29. 86 8

ATOM 1620 CB SER A 209 38. 141 11.126 -27. 751 1. 00 32. 08 6

ATOM 1621 OG SER A 209 37. 320 11.455 -26. 630 1. 00 36. 96 8

ATOM 1622 N SER A 210 40. 502 12.521 -29. 507 1. 00 31. 09 7

ATOM 1623 CA SER A 210 41. 372 12.426 -30. 703 1. 00 33. 89 6

ATOM 1624 C SER A 210 42. 826 12.447 -30. 297 1. 00 33. 77 6

ATOM 1625 O SER A 210 43. 687 11.734 -30. 842 1. 00 34. 87 8

ATOM 1626 CB SER A 210 41. 024 13.563 -31. 655 1. 00 36. 51 6

ATOM 1627 OG SER A 210 42. .171 13.743 -32. 490 1. 00 42. 40 8

ATOM 1628 N ILE A 211 43. ,172 13.190 -29. 230 1. 00 31. ,25 7

ATOM 1629 CA ILE A 211 44. ,530 13.129 -28. 705 1. 00 30. ,79 6

ATOM 1630 C ILE A 211 44. ,815 11.731 -28. 188 1. 00 31. ,65 6

ATOM 1631 O ILE A 211 45. ,878 11.124 -28. 405 1. .00 31. ,20 8

ATOM 1632 CB ILE A 211 44. ,710 14.154 -27. .580 1. ,00 30. ,45 6

ATOM 1633 CGI ILE A 211 44. .646 15.580 -28. .137 1. .00 29. .16 6

ATOM 1634 CG2 ILE A 211 46. .009 13.912 -26. .797 1. ,00 28. .20 6

ATOM 1635 CDl ILE A 211 44. .501 16.613 -27. .014 1. .00 28. .78 6

ATOM 1636 N ALA A 212 43. .882 11.162 -27. .426 1. .00 31. .19 7

ATOM 1637 CA ALA A 212 44. ,069 9.828 -26. .852 1. .00 31. .19 6

ATOM 1638 C ALA A 212 44. .251 8.789 -27. .955 1. .00 33. .70 6

ATOM 1639 O ALA A 212 45. .100 7.892 -27. .832 1. .00 34. .72 8

ATOM 1640 CB ALA A 212 42, .879 9.427 -25. .995 1. .00 31, .27 6

ATOM 1641 N ASP A 213 43, .478 8.916 -29, .045 1, .00 32, .83 7

ATOM 1642 CA ASP A 213 43 .576 7.982 -30, .167 1, .00 34 .55 6

ATOM 1643 C ASP A 213 45 .008 7.998 -30, .723 1, .00 34 .80 6

ATOM 1644 O ASP A 213 45 .616 6.938 -30, .847 1, .00 36 .87 8

ATOM 1645 CB ASP A 213 42 .567 8.322 -31, .256 1 .00 33 .87 6

ATOM 1646 CG ASP A 213 41 .145 7.900 -30, .886 1, .00 36 .07 6

ATOM 1647 ODl ASP A 213 40 .932 7.091 -29, .951 1 .00 36 .03 8

ATOM 1648 OD2 ASP A 213 40 .224 8.400 -31 .585 1, .00 36 .99 8

ATOM 1649 N LYS A 214 45 .527 9.193 -30 .994 1 .00 34 .39 7

ATOM 1650 CA LYS A 214 46 .892 9.357 -31 .506 1 .00 35 .31 6

ATOM 1651 C LYS A 214 47 .904 8.782 -30 .536 1 .00 37 .91 6

ATOM 1652 O LYS A 214 48 .900 8.106 -30 .920 1 .00 39 .73 8

ATOM 1653 CB LYS A 214 47 .196 10.833 -31 .789 1 .00 33 .06 6

ATOM 1654 .CG LYS A 214 46 .295 11.525 -32 .774 1 .00 33 .68 6

ATOM 1655 CD LYS A 214 46 .733 12.968 -33 .079 1. .00 32 .27 6

ATOM 1656 CE LYS A 214 45 .891 13.544 -34 .215 1. .00 33 .88 6

ATOM 1657 NZ LYS A 214 46 .243 14.978 -34 .497 1 .00 35 .57 7

ATOM 1658 N LEU A 215 47 .726 9.056 -29 .227 1 .00 38 .37 7

ATOM 1659 CA LEU A 215 48 .742 8.507 -28 .299 1 .00 41 .26 6

ATOM 1660 C LEU A 215 48 .676 6.988 -28 .267 1 .00 42 .76 6

ATOM 1661 O LEU A 215 49 .717 6.311 -28 .250 1 .00 43 .43 8

ATOM 1662 CB LEU A 215 48 .615 9.016 -26 .871 1 .00 38 .15 6

ATOM 1663 CG LEU A 215 48 .941 10.483 -26 .658 1 .00 39 .14 6

ATOM 1664 CDl LEU A 215 48 .406 10.973 -25 .306 1 .00 39 .20 6

ATOM . 1665 CD2 LEU A 215 50 .441 10.749 -26 .718 1 .00 39 .00 6

ATOM 1666 N GLN A 216 47 .493 6.407 -28 .253 1 .00 44 .37 7

ATOM 1667 CA GLN A 216 47 .328 4.952 -28 .225 1 .00 47 .10 6

ATOM 1668 C GLN A 216 47 .833 4.272 -29 .499 1 .00 47 .76 6

ATOM 1669 O GLN A 216 48 .153 3.081 -29 .469 1 .00 48 .80 8

ATOM 1670 CB GLN A 216 45 .859 4.643 -27 .991 1 .00 48 .55 6

ATOM 1671 CG GLN A 216 45 .452 3.303 -27 .435 1 .00 50 .81 6

ATOM 1672 CD GLN A 216 44 .259 3.444 -26 .493 1 .00 53 .17 6

ATOM 1673 OE1 GLN A 216 43 .252 4.063 -26 .856 1 .00 54 .69 8

ATOM 1674 NE2 GLN A 216 44 .354 2.898 -25 .279 1 .00 53 .81 7

ATOM 1675 N ALA A 217 47 .944 4.977 -30 .617 1 .00 47 .64 7

ATOM 1676 CA ALA A 217 48 .431 4.433 -31 .869 1 .00 48 .49 6

ATOM 1677 C ALA A 217 49 .948 4.569 -31 .997 1 .00 48 .68 6

ATOM 1678 O ALA A 217 50 .517 4.182 -33 .024 1 .00 51 .00 8 ATOM 1679 CCBB AALLAA A 217 47.789 5.138 33.060 1.00 47.,71 6

ATOM 1680 N N GGLLYY A 218 50. 612 5.211 31.056 1 .00 47. ,70 7

ATOM 1681 C CAA GGLLYY A 218 52. 037 5.390 31.027 1. .00 46. ,44 6

ATOM 1682 C C GGLLYY A 218 52. 539 6.780 31.316 1 .00 47. ,59 6

ATOM 1683 O O GLY A 218 53. 771 6. 979 -31.285 1 .00 47. . .5500 8

ATOM 1684 N N GLU A 219 51. 677 7 755 -31.607 1 .00 45.. .8899 7

ATOM 1685 C CAA GLU A 219 52. 216 9 086 -31.891 1 .00 46. .96 6

ATOM 1686 C C GLU A 219 52. 912 9 624 -30.651 1 .00 48. ,26 6

ATOM 1687 O O GLU A 219 52. 403 9 484 -29.530 1 .00 48. .86

ATOM 1688 C CBB GLU A 219 51. 146 10.071 -32.380 1 .00 47. .88

ATOM 1689 C CGG GLU A 219 50. 460 9.695 -33.672 1 .00 48. .05

ATOM 1690 C CDD G GLLUU A 2 21199 49. 744 10.817 -34.384 1 .00 50. .68

ATOM 1691 O OEE11 GGLLUU A 221199 50. 134 12.015 -34.408 1 .00 51. .01

ATOM 1692 O OEE22 GLU A 219 48. 702 10.497 -35.025 1 .00 52, .09

ATOM 1693 N N ARG A 220 54. 135 10.154 -30.831 1 .00 47, .68 7

ATOM 1694 C CAA ARG A 220 54. 868 10.698 -29.694 1 .00 47 .37 6

ATOM 1695 C C ARG A 220 55. 402 12.091 -29.989 1 .00 47 .62 6

ATOM 1696 O O ARG A 220 56. 106 12.622 -29.125 1 .00 49 .49 8

ATOM 1697 C CBB ARG A 220 56. 014 9.790 -29.239 1 .00 46 .78 6

ATOM 1698 C CGG ARG A 220 55. 570 8.463 -28.643 1 .00 46 .54 6

ATOM 1699 C CDD ARG A 220 54. 878 8.628 -27.293 1 .00 45 .80 6

ATOM 1700 N NEE ARG A 2 22200 54. 371 7.359 -26.801 1 .00 45 .04 7

ATOM 1701 C CZZ AARRGG A 222200 53. 281 6.683 -27.074 1 .00 44 .93 6

ATOM 1702 N NHHll AARRGG A 222200 52. 341 7.093 -27.930 1 .00 45 .42 7

ATOM 1703 NH2 ARG A 222200 53. 080 5.516 -26.476 1 .00 44 .28 7

ATOM 1704 N ASP A 221 54. 976 12.756 -31.052 .00 .60 7

ATOM 1705 CA ASP A 221 55. ,381 14.161 -31.242 .00 .15 6

ATOM 1706 C AASSPP A 2 22211 54. ,296 15.005 -30.557 1.00 46. 06 6

ATOM 1707 O AASSPP A 222211 53. 379 15.515 -31.197 1.00 44. 76

ATOM 1708 CB AASSPP A 222211 55. ,576 14.527 -32.691 1.00 50. 20

ATOM 1709 CG AASSPP A 222211 56. .053 15.928 -32.988 1.00 53. 21

ATOM 1710 ODl AASSPP A 222211 56. .188 16.801 -32.101 1.00 53. 81

ATOM 1711 OD2 ASP A 221 56. .309 16.204 -34.191 1.00 55. 09

ATOM 1712 N LEU A 222 54. ,465 15.167 -29.249 1.00 43. 92 7

ATOM 1713 CA LLEEUU A 2 22222 53. .451 15.829 -28.427 1.00 42. 81 6

ATOM 1714 C LLEEUU A 222222 53. ,215 17.271 -28.774 1.00 43. 64 6

ATOM 1715 O LLEEUU A 222222 52, .066 17.762 -28.789 1.00 41. 82 8

ATOM 1716 CB LEU A 222 53, .894 15.652 -26.952 1.00 43. 09 6

ATOM 1717 CG LEU A 222 54, .196 14.191 -26.578 1.00 41. 83 6

ATOM 1718 CDl LEU A 222 54 .442 14.033 -25.081 1.00 42. ,53 6

ATOM 1719 CD2 LLEEUU A 2 22222 53 .086 13.237 -26.991 1.00 41. ,15 6

ATOM 1720 N AASSPP A 222233 54 .285 18.012 -29.105 1.00 43. ,23 7

ATOM 1721 CA ASP A 223 54 .124 19.416 -29.472 1.00 44. ,33 6

ATOM 1722 C ASP A 223 53 .223 19.562 -30.688 1.00 44. ,26 6

ATOM 1723 O ASP A 223 52 .401 20.490 -30.770 1.00 45. ,10 8

ATOM 1724 CB ASP A 223 55 .508 20.042 -29.717 1.00 45. ,77 6

ATOM 1725 N GLU A 224 53 .398 18.654 -31.651 1.00 44. ,43 7

ATOM 1726 CA GLU A 224 52 .583 18.676 -32.863 1.00 45. .57 6

ATOM 1727 C GLU A 224 51 .126 18.332 -32.533 1.00 41. .13 6

ATOM 1728 O GLU A 224 50 .187 18.995 -32.967 1 1..00 40, .57 8

ATOM 1729 CB GLU A 224 53 .146 17.723 -33.915 11..00 49, .14 6

ATOM 1730 CG GLU A 224 52 .327 17.645 -35.186 11..00 53, .71 6

ATOM 1731 CD GLU A 224 52 .241 18. ,926 - 3355..9 99911 11..00 57, .27 6

ATOM 1732 OE1 GLU A 224 52 .627 20. ,028 - 3355..5 53300 11..00 58, .34

ATOM 1733 OE2 GLU A 224 51 .738 18. ,792 - 3377..1 14411 11..00 59, .44

ATOM 1734 N ILE A 225 50 .928 17. ,234 - 3311..8 83377 11..00 38, .07 7

ATOM 1735 CA ILE A 225 49 .602 16. ,821 - 3311..3 36600 11..00 36, .44 6

ATOM 1736 C ILE A 225 48 .838 17. ,929 -30. .641 11..00 35, .31 6

ATOM 1737 O ILE A 225 47 .630 18. .075 -30. .873 11..00 34 .79 8

ATOM 1738 CB ILE A 225 49 .745 15. .630 -30. .401 11..00 36 .23 6

ATOM 1739 CGI ILE A 225 50 .310 14, .449 -31. .200 11..00 36 .60 6

ATOM 1740 CG2 ILE A 225 48 .432 15, .233 -29. .722 11..00 36 .18 6

ATOM 1741 CDl ILE A 2 22255 50 .515 13. .174 -30. .428 11..00 37 .76 6

ATOM 1742 N I ILLEE A 222266 49 .522 18. .680 -29. .780 11..00 33 .53 7

ATOM 1743 CA IILLEE A 222266 48 .922 19, .759 -29. .025 11..00 33 .52 6

ATOM 1744 C IILLEE A 222266 48 .614 20. .969 -29. .881 11..00 33 .80 6

ATOM 1745 O ILE A 226 47 .581 21, .655 -29. .737 11..00 32 .30 8

ATOM 1746 CB ILE A 226 49 .877 20, .107 -27. .843 11..00 34 .98 6

ATOM 1747 CGI I ILLEE A 2 22266 49 .847 18 .937 -26, .874 11..00 34 .99 6

ATOM 1748 CG2 IILLEE A 222266 49 .490 21 .417 -27 .159 11..00 34 .94 6

ATOM 1749 CDl ILE A 226 50 .657 19.117 -25.611 1.00 36 .97 6

ATOM 1750 N THR A 227 49 .527 21.261 -30.830 1.00 33 .69 7

ATOM 1751 CA THR 227 49 .287 22.418 -31.697 1.00 34 .02 6

ATOM 1752 C THR A 227 48 .040 22.160 -32.526 1.00 32 .93 6 ATOM 1753 O THR A 227 47.183 23.034 -32.604 1.00 33.21 8

ATOM 1754 CB THR A 227 50.469 22.754 -32. 630 1.00 36. 23 6

ATOM 1755 OG1 THR A 227 51.656 22.905 -31. 839 1.00 38. 63 8

ATOM 1756 CG2 THR A 227 50.229 24.059 -33. 378 1.00 37. 54 6

ATOM 1757 N ILE A 228 47.887 20.967 -33. 060 1.00 33. 57 7

ATOM 1758 CA ILE A 228 46.742 20.647 -33. 899 1.00 33. 85 6

ATOM 1759 C ILE A 228 45.453 20.703 -33. 074 1.00 33. 32 6

ATOM 1760 O ILE A 228 44.417 21.205 -33. 482 1.00 31. 47 8

ATOM 1761 CB ILE A 228 46.908 19.275 -34. 533 1.00 36. 08 6

ATOM 1762 CGI ILE A 228 48.002 19.323 -35. 634 1.00 39. 34 6

ATOM 1763 CG2 ILE A 228 45.610 18.758 -35. 136 1.00 35. 68 6

ATOM 1764 CDl ILE A 228 48.385 17.919 -36. 092 1.00 39. 59 6

ATOM 1765 N ALA A 229 45.597 20.146 -31. 859 1.00 33. 09 7

ATOM 1766 CA ALA A 229 44.441 20.114 -30. 930 1.00 31. 53 6

ATOM 1767 C ALA A 229 43.948 21.497 -30. 607 1.00 28. 89 6

ATOM 1768 O ALA A 229 42.733 21.771 -30. 644 1.00 28. 46 8

ATOM 1769 CB ALA A 229 44.898 19.315 -29. 707 1.00 31. 42 6

ATOM 1770 N GLY A 230 44.836 22.471 -30. 407 1.00 29. 20 7

ATOM 1771 CA GLY A 230 44.485 23.857 -30. 166 1.00 30. 51 6

ATOM 1772 C GLY A 230 43.797 24.472 -31. 372 1.00 31. 48 6

ATOM 1773 O GLY A 230 42.759 25.155 -31. 288 1.00 33. 24 8

ATOM 1774 N GLN A 231 44.374 24.217 -32. 569 1.00 33. 19 7

ATOM 1775 CA GLN A 231 43.812 24.700 -33. 823 1.00 33. 48 6

ATOM 1776 C GLN A 231 42.396 24.206 -34. ,027 1.00 32. .96 6

ATOM 1777 O GLN A 231 41.476 24.995 -34. 324 1.00 34. .21 8

ATOM 1778 CB GLN A 231 44.704 24.245 -35. .003 1.00 34. ,34 6

ATOM 1779 CG GLN A 231 46.007 25.041 -35. 007 1.00 36. ,14 6

ATOM 1780 CD GLN A 231 47.002 24.556 -36. 052 1.00 38. ,53 6

ATOM 1781 OE1 GLN A 231 46.812 23.541 -36. 732 1.00 39. .14 8

ATOM 1782 NE2 GLN A 231 48.085 25.312 -36. .189 1.00 39. .12 7

ATOM 1783 N GLU A 232 42.214 22.900 -33. ,801 1.00 31. .08 7

ATOM 1784 CA GLU A 232 40.897 22.280 -33. .907 1.00 33. .90 6

ATOM 1785 C GLU A 232 39.897 22.898 -32. .923 1.00 32. .79 6

ATOM 1786 O GLU A 232 38.785 23.235 -33. ,345 1.00 30. .71 8

ATOM 1787 CB GLU A 232 40.956 20.772 -33. .659 1.00 36. .16 6

ATOM 1788 CG GLU A 232 41.681 19.963 -34. .705 1.00 40. .99 6

ATOM 1789 CD GLU A 232 41.956 18.526 -34. .336 1.00 43, .88 6

ATOM 1790 OEl GLU A 232 42.231 18.222 -33. .162 1.00 46. .75 8

ATOM 1791 OE2 GLU A 232 41.978 17.624 -35. .213 1.00 46, .96 8

ATOM 1792 N LEU A 233 40.279 23.075 -31, .654 1.00 31 .79 7

ATOM 1793 CA LEU A 233 39.390 23.738 -30, .717 1.00 31 .75 6

ATOM 1794 C LEU A 233 39.053 25.159 -31, .151 1.00 30 .93 6

ATOM 1795 O LEU A 233 37.914 25.617 -31, .117 1.00 29 .58 8

ATOM 1796 CB LEU A 233 40.002 23.804 -29, .306 1.00 28 .67 6

ATOM 1797 CG LEU A 233 40.122 22.439 -28, .598 1.00 29 .48 6

ATOM 1798 CDl LEU A 233 41.084 22.505 -27 .425 1.00 29 .09 6

ATOM 1799 CD2 LEU A 233 38.712 21.976 -28 .189 1.00 30 .10 6

ATOM 1800 N ASN A 234 40.083 25.889 -31 .615 1.00 32 .79 7

ATOM 1801 CA ASN A 234 39.861 27.288 -32 .011 1.00 33 .77 6

ATOM 1802 C ASN A 234 38.946 27.388 -33 .220 1.00 31 .44 6

ATOM 1803 O ASN A 234 38.071 28.254 -33 .258 1.00 32 .82 8

ATOM 1804 CB ASN A 234 41.220 27.972 -32 .243 1.00 36 .16 6

ATOM 1805 CG ASN A 234 41.890 28.295 -30 .919 1.00 39 .98 6

ATOM 1806 ODl ASN A 234 41.296 28.257 -29 .838 1.00 40 .76 8

ATOM 1807 ND2 ASN A 234 43.185 28.592 -30 .922 1.00 39 .55 7

ATOM 1808 N GLU A 235 39.068 26.440 -34 .127 1.00 31 .44 7

ATOM 1809 CA GLU A 235 38.223 26.392 -35 .306 1.00 34 .68 6

ATOM 1810 C GLU A 235 36.779 26.082 -34 .971 1.00 34 .35 6

ATOM 1811 O GLU A 235 35.878 26.565 -35 .629 1.00 35 .56 8

ATOM 1812 CB GLU A 235 38.763 25.314 -36 .244 1.00 36 .35 6

ATOM 1813 N LYS A 236 36.532 25.307 -33 .908 1.00 36 .15 7

ATOM 1814 CA LYS A 236 35.169 24.977 -33 .488 1.00 35 .47 6

ATOM 1815 C LYS A 236 34.483 26.106 -32 .738 1.00 34 .87 6

ATOM 1816 0 LYS A 236 33.253 26.085 -32 .561 1.00 36 .38 8

ATOM 1817 CB LYS A 236 35.213 23.748 -32 .577 1.00 37 .47 6

ATOM 1818 CG LYS A 236 35.609 22.450 -33 .245 1.00 38 .51 6

ATOM 1819 CD LYS A 236 35.643 21.345 -32 .192 1.00 40 .94 6

ATOM 1820 CE LYS A 236 36.184 20.083 -32 .827 1.00 42 .93 6

ATOM 1821 NZ LYS A 236 36.231 18.973 -31 .850 1.00 45 .15 7

ATOM 1822 N GLY A 237 35.225 27.094 -32 .274 1.00 33 .61 7

ATOM 1823 CA GLY A 237 34.660 28.241 -31 .576 1.00 33 .28 6

ATOM 1824 C GLY A 237 35.127 28.401 -30 .157 1.00 32 .89 6

ATOM 1825 O GLY A 237 34.644 29.291 -29 .429 1.00 36 .87 8

ATOM 1826 N PHE A 238 36.017 27.546 -29 .668 1.00 30 .90 7 r--

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ATOM 1901 CA ASP A 247 52.753 10.248 -17.537 1.00 34.88 6

ATOM 1902 C ASP A 247 51. 652 10. 087 -16. 495 1. 00 31. 75 6

ATOM 1903 O ASP A 247 51. 690 10. 908 -15. 584 1. 00 32. 95 8

ATOM 1904 CB ASP A 247 54. 146 9. 952 -16. 954 1. 00 37. 68 6

ATOM 1905 CG ASP A 247 54. 195 8. 479 -16. 611 1. 00 39. 66 6

ATOM 1906 ODl ASP A 247 53. 482 8. 015 -15. 710 1. 00 41. 79 8

ATOM 1907 OD2 ASP A 247 54. 924 7. 748 -17. 284 1. 00 42. 94 8

ATOM 1908 N ALA A 248 50. 712 9. 185 -16. 600 1. 00 33. 81 7

ATOM 1909 CA ALA A 248 49. 616 9. 156 -15. 609 1. 00 32. 51 6

ATOM 1910 C ALA A 248 50. 041 8. 675 -14. 232 1. 00 34. 35 6

ATOM 1911 O ALA A 248 49. 399 9. 063 -13. 249 1. 00 33. 85 8

ATOM 1912 CB ALA A 248 48. 499 8. 253 -16. 070 1. 00 33. 01 6

ATOM 1913 N ASP A 249 51. 057 7. 825 -14. 103 1. 00 36. 10 7

ATOM 1914 CA ASP A 249 51. 462 7. 281 -12. 822 1. 00 35. 70 6

ATOM 1915 C ASP A 249 52. 421 8. 185 -12. 073 1. 00 33. 40 6

ATOM 1916 O ASP A 249 52. 399 8. 230 -10. 818 1. 00 31. 30 8

ATOM 1917 CB ASP A 249 52. 152 5. 916 -13. 031 1. 00 39. 11 6

ATOM 1918 CG ASP A 249 51. 137 5. 007 -13. 715 1. 00 43. 20 6

ATOM 1919 ODl ASP A 249 50. 028 4. 826 -13. .134 1. 00 45. 31 8

ATOM 1920 OD2 ASP A 249 51. 423 4. 514 -14. 817 1. 00 43. 99 8

ATOM 1921 N THR A 250 53. .275 8. 844 -12. ,857 1. ,00 31. ,16 7

ATOM 1922 CA THR A 250 54, .301 9. .667 -12. ,240 1. ,00 32. ,87 6

ATOM 1923 C THR A 250 54. 087 11. 144 -12. ,416 1. ,00 32. ,81 6

ATOM 1924 O THR A 250 54. ,760 11. ,935 -11. ,789 1. ,00 30. ,56 8

ATOM 1925 CB THR A 250 55, ,740 9. 378 -12. ,792 1. ,00 34. ,12 6

ATOM 1926 OG1 THR A 250 55. ,779 9. .795 -14 . ,158 1. ,00 34. ,42 8

ATOM 1927 CG2 THR A 250 56. .080 7. .911 -12. .637 1. .00 34. ,28 6

ATOM 1928 N LEU A 251 53. .281 11. .587 -13. .365 1. ,00 32. .56 7

ATOM 1929 CA LEU A 251 52. .972 12. ,978 -13. .672 1. ,00 34. .35 6

ATOM 1930 C LEU A 251 54. .124 13. .689 -14. .360 1. .00 35. .41 6

ATOM 1931 O LEU A 251 54. .093 14. .893 -14, .592 1. .00 35. .99 8

ATOM 1932 CB LEU A 251 52, .494 13. .758 -12. .418 1. .00 33, .68 6

ATOM 1933 CG LEU A 251 51, .220 13. .147 -11, .792 1. .00 34. .55 6

ATOM 1934 CDl LEU A 251 50. .797 13. .969 -10. .573 1. .00 35. .91 6

ATOM 1935 CD2 LEU A 251 50, .101 13. .012 -12, .821 1. .00 35. .43 6

ATOM 1936 N LEU A 252 55, .194 12, .962 -14, .695 1, .00 39, .58 7

ATOM 1937 CA LEU A 252 56. .323 13. .507 -15, .418 1. .00 40, .96 6

ATOM 1938 C LEU A 252 55, .945 13, .614 -16, .874 1, .00 43, .27 6

ATOM 1939 O LEU A 252 54, .906 13. .129 -17, .318 1, .00 40, .97 8

ATOM 1940 CB LEU A 252 57, ,550 12, .584 -15, .264 1, .00 42, .55 6

ATOM 1941 CG LEU A 252 58. .072 12. .496 -13. .823 1, .00 43, .46 6

ATOM 1942 CDl LEU A 252 59, .196 11, .476 -13. .685 1, .00 44, .26 6

ATOM 1943 CD2 LEU A 252 58 .546 13, .868 -13 .341 1, .00 43 .34 6

ATOM 1944 N GLU A 253 56, .855 14, .189 -17, .659 1, .00 46, .27 7

ATOM 1945 CA GLU A 253 56, .716 14, .144 -19 .109 1, .00 48 .94 6

ATOM 1946 C GLU A 253 56, .642 12, .706 -19, .612 1, .00 48, .01 6

ATOM 1947 O GLU A 253 57 .291 11, .928 -18 .871 1, .00 48 .08 8

ATOM 1948 CB GLU A 253 57 .877 14 .878 -19 .783 1, .00 52 .86 6

ATOM 1949 CG GLU A 253 57 .914 16 .371 -19 .500 1, .00 57 .25 6

ATOM 1950 CD GLU A 253 56 .720 17 .104 -20 .077 1 .00 60 .45 6

ATOM 1951 OE1 GLU A 253 56 .308 16 .771 -21 .207 1 .00 61 .73 8

ATOM 1952 OE2 GLU A 253 56 .194 18 .011 -19 .397 1 .00 61 .77 8

ATOM 1953 N VAL A 254 55 .835 12 .324 -20 .596 1 .00 48 .66 7

ATOM 1954 CA VAL A 254 55 .849 10 .887 -20 .872 1 .00 49 .85 6

ATOM 1955 C VAL A 254 57 .149 10 .638 -21 .614 1 .00 51 .30 6

ATOM 1956 O VAL A 254 57 .658 11 .494 -22 .340 1 .00 49 .27 8

ATOM 1957 CB VAL A 254 54 .576 10 .399 -21 .614 1 .00 51 .06 6

ATOM 1958 CGI VAL A 254 53 .600 11 .541 -21 .825 1 .00 50 .21 6

ATOM 1959 CG2 VAL A 254 54 .935 9 .757 -22 .940 1 .00 51 .39 6

ATOM 1960 N SER A 255 57 .636 9 .432 -21 .398 1 .00 50 .78 7

ATOM 1961 CA SER A 255 58 .878 8 .951 -21 .946 1 .00 52 .29 6

ATOM 1962 C SER A 255 58 .718 7 .516 -22 .423 1 .00 53 .07 6

ATOM 1963 O SER A 255 57 .625 6 .965 -22 .444 1 .00 53 .08 8

ATOM 1964 CB SER A 255 59 .978 8 .985 -20 .878 1 .00 51 .99 6

ATOM 1965 OG SER A 255 59 .761 7 .859 -20 .013 1 .00 51 .83 8

ATOM 1966 N GLU A 256 59 .844 6 .858 -22 .692 1 .00 55 .01 7

ATOM 1967 CA GLU A 256 59 .903 5 .485 -23 .155 1 .00 55 .63 6

ATOM 1968 C GLU A 256 59 .251 4 .493 -22 .207 1 .00 55 .82 6

ATOM 1969 O GLU A 256 58 .566 3 .543 -22 .591 1 .00 55 .91 8

ATOM 1970 CB GLU A 256 61 .380 5 .091 -23 .350 1 .00 56 .43 6

ATOM 1971 N THR A 257 59 .458 4 .732 -20 .919 1 .00 55 .14 7

ATOM 1972 CA THR A 257 58 .921 3 .928 -19 .846 1 .00 54 .05 6

ATOM 1973 C THR A 257 57 .443 4 .151 -19 .554 1 .00 51 .69 6

ATOM 1974 0 THR A 257 56 .836 3 .301 -18 .887 1 .00 51 .58 8 ATOM 1975 CB THR A 257 59.723 4.223 -18.554 00 55.07 ATOM 1976 OG1 THR A 257 59.404 5.533 -18.065 00 56.77 ATOM 1977 CG2 THR A 257 61.215 4.150 -18.828 00 55.65 ATOM 1978 N SER A 258 56.834 5.252 -20.000 00 49.85 ATOM 1979 CA SER A 258 55.426 481 -19.663 00 46.23 ATOM 1980 C SER A 258 54.484 382 -20.104 00 46.46 ATOM 1981 0 SER A 258 54.511 984 -21.269 00 47.83 ATOM 1982 CB SER A 258 54.950 783 -20.306 00 44.06 ATOM 1983 OG SER A 258 55.742 841 -19.839 00 40.94 ATOM 1984 N LYS A 259 53.626 905 -19.221 00 46.05 7 ATOM 1985 CA LYS A 259 52.624 902 -19.512 00 46.69 6 ATOM 1986 C LYS A 259 51.252 3.551 -19.739 1.00 45.85 6 ATOM 1987 0 LYS A 259 50.329 3.046 -20.369 00 45.29 8 ATOM 1988 CB LYS A 259 52.455 1. .886 -18.382 00 46.44 6 ATOM 1989 CG LYS A 259 53.726 1. ,200 -17.920 00 47.93 6 ATOM 1990 N ARG A 260 51.088 4. .696 -19.069 00 46.77 7 ATOM 1991 CA ARG A 260 49.800 5. .397 -19.104 00 45.39 6 ATOM 1992 C ARG A 260 49.991 6. .882 -19.278 00 41.75 6 ATOM 1993 O ARG A 260 50.970 7. .421 -18.763 00 41.96 8 ATOM 1994 CB ARG A 260 49.004 5. .146 -17.814 00 48.72 6 ATOM 1995 CG ARG A 260 48.340 3. 797 -17.715 1.00 52.78 6 ATOM 1996 CD ARG A 260 47.783 3. 490 -16.342 1.00 56.11 6 ATOM 1997 NE ARG A 260 48.800 3, 016 -15.423 1.00 60.02 7 ATOM 1998 CZ ARG A 260 49.366 1.817 -15.362 1.00 61.86 6 ATOM 1999 NHl ARG A 260 49.066 0.806 -16.179 1.00 62.97 7

ATOM 2000 NH2 ARG A 260 50.275 1.615 -14.410 1.00 62.19 7 ATOM 2001 N ALA A 261 49.079 7.547 -20.024 1.00 39.42 7 ATOM 2002 CA ALA A 261 49.232 8.993 -20.107 1.00 35.31 6 ATOM 2003 C ALA A 261 47.928 9.630 -19.612 1.00 32.26 6 ATOM 2004 O ALA A 261 46.872 9.005 -19.790 00 34.66 8

ATOM 2005 CB ALA A 261 49.538 9.504 -21.504 00 34.95 6 ATOM 2006 N VAL A 262 48.060 10.831 -19.087 00 29.67 7 ATOM 2007 CA VAL A 262 46.852 11.578 -18.705 00 27.51 6 ATOM 2008 C VAL A 262 46.916 12.796 -19.608 1.00 27.97 6 ATOM 2009 O VAL A 262 47.977 13.414 -19.791 00 26.28 8 ATOM 2010 CB VAL A 262 46.750 11.979 -17.233 00 29.25 6 ATOM 2011 CGI VAL A 262 47.995 12.725 -16.785 00 30.58 6 ATOM 2012 CG2 VAL A 262 45.527 12.884 -16.976 1.00 30.36 6 ATOM 2013 N ILE A 263 45.801 13.185 -20.185 00 26.21 7 ATOM 2014 CA ILE A 263 45.639 14.343 -21.031 00 26.33 6

ATOM 2015 C ILE A 263 44.738 15.341 -20.300 1.00 28.09 6 ATOM 2016 O ILE A 263 43.635 14.903 -19.935 00 26.14 8 ATOM 2017 CB ILE A 263 44.977 13.970 -22.357 00 27.18 6 ATOM 2018 CGI ILE A 263 45.701 12.767 -22.999 00 30.42 6 ATOM 2019 CG2 ILE A 263 44.931 15.184 -23.302 00 26.41 6

ATOM 2020 CDl ILE A 263 44.751 11.943 -23.867 00 32.55 6 ATOM 2021 N LEU A 264 45.198 16.564 -20.149 00 28.73 7 ATOM 2022 CA LEU A 264 44.453 17.626 -19.514 00 30.58 6 ATOM 2023 C LEU A 264 44.108 18.698 -20.530 1.00 29.44 6 ATOM 2024 O LEU A 264 45.005 19.177 -21.235 00 30.50 8

ATOM 2025 CB LEU A 264 45.273 18.264 -18.392 00 33.45 6 ATOM 2026 CG LEU A 264 46.310 17.397 -17.677 00 35.36 6 ATOM 2027 CDl LEU A 264 47.287 18.261 -16.855 00 38.43 6 ATOM 2028 CD2 LEU A 264 45.634 16.357 -16.800 00 36.22 6 ATOM 2029 N VAL A 265 42.875 19.166 -20.643 00 28.12 7 ATOM 2030 CA VAL A 265 42.516 20.228 -21.586 00 30.77 6 ATOM 2031 C VAL A 265 41.662 21.288 -20.868 00 30.38 6 ATOM 2032 O VAL A 265 40.888 20.946 -19.964 00 33.23 8 ATOM 2033 CB VAL A 265 41.740 19.716 -22.798 00 30.45 6 TOM 2034 CGI VAL A 265 42.546 18.732 -23.649 00 31.64 6

ATOM 2035 CG2 VAL A 265 40.456 18.962 -22.415 00 30.65 6 ATOM 2036 N ALA A 266 41.822 22.538 -21.233 00 30.29 7 ATOM 2037 CA ALA A 266 40.992 23.628 -20.697 1.00 27.93 6 ATOM 2038 C ALA A 266 40.722 24.514 -21.890 ,00 28.75 6 TOM 2039 O ALA A 266 41.687 24.771 -22.653 ,00 31.65 8

ATOM 2040 CB ALA A 266 41.637 24.388 -19.574 ,00 28.93 6 ATOM 2041 N ALA A 267 39.535 25.012 -22.069 .00 27.14 7 ATOM 2042 CA ALA A 267 39.237 25.880 -23.189 .00 28.13 6 ATOM 2043 C ALA A 267 38.051 26.744 -22.796 .00 29.67 6 TOM 2044 O ALA A 267 37.054 26.257 -22.261 1.00 27.60 8

ATOM 2045 CB ALA A 267 38.861 25.167 -24.478 1.00 26.05 6 ATOM 2046 N TRP A 268 38.151 28.007 -23.166 1.00 29.63 7 ATOM 2047 CA TRP A 268 37.074 28.951 -22.969 1.00 28.26 6 ATOM 2048 C TRP A 268 36.049 28.766 -24.072 1.00 29.88 6 ATOM 2049 0 TRP A 268 36 . 407 28 . 609 -25 . 245 1 . 00 30 . 20

ATOM 2050 CB TRP A 268 37.599 30.394 -22.996 1.00 30. 40 6

ATOM 2051 CG TRP A 268 38.406 30.735 -21.778 1.00 31. 50 6

ATOM 2052 CDl TRP A 268 39.756 30.638 -21.572 1.00 32. 04 6

ATOM 2053 CD2 TRP A 268 37.850 31.336 -20.602 1.00 29. 94 6

ATOM 2054 NE1 TRP A 268 40.071 31.097 -20.307 1.00 32. 09 7

ATOM 2055 CE2 TRP A 268 38.905 31.521 -19.699 1.00 32. 20 6

ATOM 2056 CE3 TRP A 268 36.543 31.660 -20.214 1.00 29. 41 6

ATOM 2057 CZ2 TRP A 268 38.729 32.062 -18.420 1.00 30. 97 6

ATOM 2058 CZ3 TRP A 268 36.362 32.188 -18.965 1.00 30. 37 6

ATOM 2059 CH2 TRP A 268 37.448 32.390 -18.097 1.00 29. 74 6

ATOM 2060 N LEU A 269 34.789 28.947 -23.715 1.00 28. 17 7

ATOM 2061 CA LEU A 269 33.648 28.954 -24.579 1.00 29. 03 6

ATOM 2062 C LEU A 269 32.680 29.913 -23.885 1.00 29. 91 6

ATOM 2063 O LEU A 269 32.201 29.674 -22.758 1.00 25. 57 8

ATOM 2064 CB LEU A 269 33.139 27.528 -24.786 1.00 30. 48 6

ATOM 2065 CG LEU A 269 31.952 27.443 -25.719 1.00 31. 96 6

ATOM 2066 CDl LEU A 269 32.337 27.993 -27.103 1.00 30. 89 6

ATOM 2067 CD2 LEU A 269 31.423 26.003 -25.790 1.00 31. 19 6

ATOM 2068 N GLY A 270 32.559 31.132 -24.446 1.00 29. 19 7

ATOM 2069 CA GLY A 270 31.738 32.156 -23.798 1.00 29. 83 6

ATOM 2070 C GLY A 270 32.341 32.563 -22.463 1.00 32. 39 6

ATOM 2071 O GLY A 270 33.549 32.829 -22.369 1.00 32. 69 8

ATOM 2072 N ASP A 271 31.552 32.562 -21.390 1.00 30. 56 7

ATOM 2073 CA ASP A 271 32.088 32.888 -20.075 1.00 31. 93 6

ATOM 2074 C ASP A 271 32.450 31.649 -19.271 1.00 31. 25 6

ATOM 2075 O ASP A 271 32.749 31.710 -18.079 1.00 30. 60 8

ATOM 2076 CB ASP A 271 31.087 33.758 -19.289 1.00 33. 98 6

ATOM 2077 CG ASP A 271 31.073 35.165 -19.921 1.00 37. 85 6

ATOM 2078 ODl ASP A 271 32.103 35.682 -20.401 1.00 38. 52 8

ATOM 2079 OD2 ASP A 271 29.996 35.770 -19.944 1.00 39. ,53 8

ATOM 2080 N ALA A 272 32.462 30.482 -19.903 1.00 29. ,77 7

ATOM 2081 CA ALA A 272 32.828 29.254 -19.228 1.00 27. .77 6

ATOM 2082 C ALA A 272 34.256 28.826 -19.557 1.00 26, .45 6

ATOM 2083 O ALA A 272 34.545 28.837 -20.745 1.00 26. .44 8

ATOM 2084 CB ALA A 272 31.977 28.068 -19.666 1.00 27, .56 6

ATOM 2085 N ARG A 273 35.053 28.448 -18.602 1.00 25. .11 7

ATOM 2086 CA ARG A 273 36.354 27.839 -18.859 1.00 25. .96 6

ATOM 2087 C ARG A 273 36.194 26.346 -18.606 1.00 23, .79 6

ATOM 2088 O ARG A 273 36.292 25.868 -17.465 1.00 25, .36 8

ATOM 2089 CB ARG A 273 37.467 28.400 -17.962 1.00 27, .51 6

ATOM 2090 CG ARG A 273 38.864 27.853 -18.355 1.00 27. .52 6

ATOM 2091 CD ARG A 273 39.848 28.605 -17.421 1.00 28, .40 6

ATOM 2092 NE ARG A 273 41.215 28.212 -17.720 0.50 26, .25 7

ATOM 2093 CZ ARG A 273 41.850 27.144 -17.306 0.50 26, .10 6

ATOM 2094 NHl ARG A 273 41.229 26.281 -16.517 0.50 28 .04 7

ATOM 2095 NH2 ARG A 273 43.107 26.909 -17.691 0.50 25 .33 7

ATOM 2096 N LEU A 274 35.918 25.587 -19.693 1.00 25 .09 7

ATOM 2097 CA LEU A 274 35.608 24.173 -19.545 1.00 23 .10 6

ATOM 2098 C LEU A 274 36.845 23.385 -19.359 1.00 23 .02 6

ATOM 2099 O LEU A 274 37.846 23.706 -20.001 1.00 24 .38 8

ATOM 2100 CB LEU A 274 34.863 23.714 -20.847 1.00 22 .40 6

ATOM 2101 CG LEU A 274 33.548 24.488 -21.045 1.00 22 .92 6

ATOM 2102 CDl LEU A 274 32.953 24.119 -22.368 1.00 25 .59 6

ATOM 2103 CD2 LEU A 274 32.619 24.185 -19.846 1.00 24 .66 6

ATOM 2104 N ILE A 275 36.844 22.342 -18.576 1.00 22 .01 7

ATOM 2105 CA ILE A 275 37.965 21.529 -18.235 1.00 24 .38 6

ATOM 2106 C ILE A 275 37.640 20.072 -18.439 1.00 24 .31 6

ATOM 2107 O ILE A 275 36.504 19.675 -18.126 1.00 23 .32 8

ATOM 2108 CB ILE A 275 38.290 21.785 -16.743 1.00 27 .33 6

ATOM 2109 CGI ILE A 275 38.853 23.233 -16.577 1.00 30 .12 6

ATOM 2110 CG2 ILE A 275 39.295 20.826 -16.161 1.00 32 .15 6

ATOM 2111 CDl ILE A 275 38.634 23.632 -15.112 1.00 33 .95 6

ATOM 2112 N ASP A 276 38.611 19.282 -18.865 1.00 23 .56 7

ATOM 2113 CA ASP A 276 38.347 17.845 -19.005 1.00 24 .73 6

ATOM 2114 C ASP A 276 39.702 17.125- -18.966 1.00 24 .26 6

ATOM 2115 O ASP A 276 40.768 17.741 -19.153 1.00 24 .98 8

ATOM 2116 CB ASP A 276 37.551 17.545 -20.271 1.00 24 .30 6

ATOM 2117 CG ASP A 276 36.730 16.276 -20.290 1.00 26 .28 6

ATOM 2118 ODl ASP A 276 36.927 15.468 -19.324 1.00 27 .91 8

ATOM 2119 OD2 ASP A 276 35.946 16.119 -21.251 1.00 25 .73 8

ATOM 2120 N ASN A 277 39.671 15.855 -18.697 1.00 22 .14 7

ATOM 2121 CA ASN A 277 40.857 15.020 -18.682 1.00 25 .69 6

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ATOM 2337 SD MET B 19 40.253 -19.824 8.206 1.00 21.29 16 ATOM 2338 CE MET B 19 41. 816 -20.143 7. 368 1.00 22. 90 6 ATOM 2339 N GLU B 20 41. 516 -17.512 10. 731 1.00 18. 16 7 ATOM 2340 CA GLU B 20 41. 687 -18.429 11. 858 1.00 20. 12 6 ATOM 2341 C GLU B 20 41. 280 -17.732 13. 182 1.00 20. 85 6 ATOM 2342 O GLU B 20 41. 156 -18.387 14. 243 1.00 24. 28 8 ATOM 2343 CB GLU B 20 43. 113 -18.960 11. 945 1.00 18. 82 6 ATOM 2344 CG GLU B 20 43. 467 -19.977 10. 846 1.00 21. 83 6 ATOM 2345 CD GLU B 20 44. 911 -20.433 10. 890 1.00 26. 79 6 ATOM 2346 OE1 GLU B 20 45. 611 -20.063 11. 869 1.00 28. 93 8 ATOM 2347 OE2 GLU B 20 45. 312 -21.210 9. 985 1.00 26. 44 8 ATOM 2348 N GLY B 21 41. 236 -16.424 13. 172 1.00 21. 16 7 ATOM 2349 CA GLY B 21 40. 877 -15.568 14. 299 1.00 20. 08 6 ATOM 2350 C GLY B 21 42. 055 -15.540 15. 311 1.00 21. 45 6 ATOM 2351 O GLY B 21 41. 856 -15.580 16. 546 1.00 20. 95 8 ATOM 2352 N LYS B 22 43. 279 -15.515 14. 815 1.00 17. 96 7 ATOM 2353 CA LYS B 22 44 . 458 -15.503 15. 668 1.00 21. 37 6 ATOM 2354 C LYS B 22 44. 924 -14.091 15. 953 1.00 23. 78 6 ATOM 2355 O LYS B 22 44. 942 -13.267 15. 041 1.00 24. 76 8 ATOM 2356 CB LYS B 22 45. 638 -16.191 14. 984 1.00 22. 71 6 ATOM 2357 CG LYS B 22 45. 420 -17.662 14. 646 1.00 25. 81 6 ATOM 2358 CD LYS B 22 45. 337 -18.553 15. 836 1.00 28. 29 6 ATOM 2359 CE LYS B 22 44. 963 -19.997 15. 550 1.00 33. 33 6 ATOM 2360 NZ LYS B 22 45. ,832 -20.715 14. ,575 1.00 29. ,69 7 ATOM 2361 N ARG B 23 45. .285 -13.775 17. ,175 1.00 19. ,63 7

ATOM 2362 CA ARG B 23 45. ,917 -12.467 17. ,446 1.00 22. ,19 6 ATOM 2363 C ARG B 23 47. .415 -12.521 17. ,203 1.00 20. ,99 6 ATOM 2364 O ARG B 23 48. ,014 -13.529 17. .533 1.00 22. 27 8 ATOM 2365 CB ARG B 23 45. ,620 -12.042 18, ,877 1.00 23. ,98 6 ATOM 2366 CG ARG B 23 44 . .149 -11.748 19. 161 1.00 33. .05 6 ATOM 2367 CD ARG B 23 43. .965 -11.207 20. .600 1.00 35. .95 6 ATOM 2368 NE ARG B 23 44. .774 -11.865 21. .560 1.00 39. .00 7 ATOM 2369 CZ ARG B 23 45, .045 -12.903 22, .319 1.00 38. .30 6 ATOM 2370 NHl ARG B 23 44. .343 -14.060 22, .457 1.00 34. .37 7 ATOM 2371 NH2 ARG B 23 46. .204 -12.653 22. .881 1.00 33. .10 7

ATOM 2372 N VAL B 24 47, .873 -11.534 16. .444 1.00 19. .44 7 ATOM 2373 CA VAL B 24 49, .260 -11.534 15. .984 1.00 19. .87 6 ATOM 2374 C VAL B 24 50, .133 -10.493 16. .615 1.00 20. .77 6 ATOM 2375 O VAL B 24 49, .724 -9.356 16, .770 1.00 20, .17 8 ATOM 2376 CB VAL B 24 49. .220 -11.301 14, .473 1.00 20, .82 6

ATOM 2377 CGI VAL B 24 50 .587 -11.071 13 .856 1.00 21, .58 6 ATOM 2378 CG2 VAL B 24 48 .493 -12.516 13 .838 1.00 22 .44 6 ATOM 2379 N ALA B 25 51. .327 -10.950 17, .072 1.00 18, .32 7 ATOM 2380 CA ALA B 25 52 .294 -9.989 17, .591 1.00 18 .65 6 TOM 2381 C ALA B 25 53 .431 -9.885 16, .600 1.00 22, .09 6 ATOM 2382 O ALA B 25 53 .908 -10.915 16, .053 1.00 26 .60 8 ATOM 2383 CB ALA B 25 52 .871 -10.371 18 .953 1.00 20 .06 6 ATOM 2384 N LEU B 26 53 .922 -8.705 16 .329 1.00 18 .28 7 ATOM 2385 CA LEU B 26 54 .997 -8.468 15 .410 1.00 16 .76 6 ATOM 2386 C LEU B 26 56 .273 -8.010 16 .156 1.00 20 .96 6 ATOM 2387 O LEU B 26 56 .139 -7.157 17 .020 1.00 21 .27 8 ATOM 2388 CB LEU B 26 54 .673 -7.425 14 .340 1.00 19 .09 6 ATOM 2389 CG LEU B 26 55 .816 -6.890 13 .487 1.00 19 .40 6 ATOM 2390 CDl LEU B 26 56 .464 -7.969 12 .603 1.00 21 .45 6 ATOM 2391 CD2 LEU B 26 55 .320 -5.738 12 .604 1.00 22 .40 6 ATOM 2392 N VAL B 27 57 .396 -8.642 15 .874 1.00 20 .49 7 ATOM 2393 CA VAL B 27 58 .684 -8.136 16 .430 1.00 19 .53 6 ATOM 2394 C VAL B 27 59 .576 -7.694 15 .308 1.00 21 .55 6 ATOM 2395 O VAL B 27 60 .170 -8.516 14 .520 1.00 22 .20 8 ATOM 2396 CB VAL B 27 59 .378 -9.239 17 .253 1.00 21 .88 6 ATOM 2397 CGI VAL B 27 60 .658 -8.617 17 .884 1.00 21 .20 6 ATOM 2398 CG2 VAL B 27 58 .513 -9.837 18 .318 1.00 20 .54 6 ATOM 2399 N PRO B 28 59 .761 -6.435 14 .910 1.00 20 .58 7 ATOM 2400 CA PRO B 28 60 .557 -5.881 13 .878 1.00 21 .31 6 ATOM 2401 C PRO B 28 62 .068 -5.886 14 .202 1.00 24 .78 6 ATOM 2402 O PRO B 28 62 .428 -5.538 15 .336 1.00 26 .50 8 ATOM 2403 CB PRO B 28 60 .112 -4.424 13 .720 1.00 22 .66 6 ATOM 2404 CG PRO B 28 58 .741 -4.426 14 .395 1.00 20 .85 6 ATOM 2405 CD PRO B 28 58 .946 -5.327 15 .578 1.00 20 .40 6 ATOM 2406 N THR B 29 62 .875 -6.483 13 .317 1.00 26 .26 7 ATOM 2407 CA THR B 29 64 .329 -6.556 13 .614 1.00 25 .08 6 ATOM 2408 C THR B 29 65 .126 -6.328 12 .359 1.00 25 .98 6 ATOM 2409 O THR B 29 64 .643 -6.415 11 .228 1.00 23 .47 8 ATOM 2410 CB THR B 29 64 .820 -7.900 14 .201 1.00 26 .97 6 ATOM 2411 OG1 THR B 29 65.022 -8.817 13.088 1.00 26.74 8

ATOM 2412 CG2 THR B 29 63.914 -8.579 15.219 1.00 25.95 6

ATOM 2413 N MET B 30 66.471 -6.078 12.560 1.00 25.32 7

ATOM 2414 CA MET B 30 67.357 -5.995 11.415 1.00 26.82 6

ATOM 2415 C MET B 30 68.261 -7.249 11.384 1.00 28.96 6

ATOM 2416 O MET B 30 69.347 -7.183 10.815 1.00 30.56 8

ATOM 2417 CB MET B 30 68.229 -4.738 11.416 1.00 26.43 6

ATOM 2418 CG MET B 30 67.252 -3.504 11.203 1.00 27.24 6

ATOM 2419 SD MET B 30 67.969 -2.187 10.263 1.00 28.19 16

ATOM 2420 CE MET B 30 69.323 -1.713 11.388 1.00 33.08 6

ATOM 2421 N GLY B 31 67.793 -8.340 11.934 1.00 27.82 7

ATOM 2422 CA GLY B 31 68.599 -9.593 11.926 1.00 29.40 6

ATOM 2423 C GLY B 31 69.833 -9.495 12.829 1.00 31.29 6

ATOM 2424 O GLY B 31 69.934 -8.645 13.713 1.00 28.83 8

ATOM 2425 N ASN B 32 70.728 -10.486 12.690 1.00 31.40 7

ATOM 2426 CA ASN B 32 71.923 -10.565 13.552 1.00 33.60 6

ATOM 2427 C ASN B 32 71.454 -10.664 14.982 1.00 30.00 6

ATOM 2428 O ASN B 32 71.870 -9.961 15.906 1.00 32.23 8

ATOM 2429 CB ASN B 32 72.857 -9.379 13.347 1.00 35.71 6

ATOM 2430 CG ASN B 32 74.231 -9.610 13.979 1.00 39.99 6

ATOM 2431 ODl ASN B 32 74.920 -8.633 14.294 1.00 42.85 8

ATOM 2432 ND2 ASN B 32 74.607 -10.864 14.228 1.00 40.08 7

ATOM 2433 N LEU B 33 70.506 -11.572 15.191 1.00 30.19 7

ATOM 2434 CA LEU B 33 69.833 -11.774 16.449 1.00 29.02 6

ATOM 2435 C LEU B 33 70.684 -12.343 17.566 1.00 35.03 6

ATOM 2436 O LEU B 33 71.521 -13.207 17.312 1.00 36.34 8

ATOM 2437 CB LEU B 33 68.616 -12.717 16.279 1.00 30.07 6

ATOM 2438 CG LEU B 33 67.670 -12.217 15.191 1.00 29.98 6

ATOM 2439 CDl LEU B 33 66.434 -13.121 15.083 1.00 31.08 6

ATOM 2440 CD2 LEU B 33 67.221 -10.777 15.431 1.00 28.84 6

ATOM 2441 N HIS B 34 70.295 -11.945 18.774 1.00 35.85 7

ATOM 2442 CA HIS B 34 71.004 -12.381 19.965 1.00 39.05 6

ATOM 2443 C HIS B 34 69.976 -12.567 21.067 1.00 37.94 6

ATOM 2444 O HIS B 34 68.762 -12.451 20.791 1.00 37.26 8

ATOM 2445 CB HIS B 34 72.097 -11.404 20.404 1.00 40.15 6

ATOM 2446 CG HIS B 34 71.668 -10.006 20.714 1.00 42.43 6

ATOM 2447 ND1 HIS B 34 70.876 -9.671 21.799 1.00 44.12 7

ATOM 2448 CD2 HIS B 34 71.953 -8.848 20.062 1.00 43.13 6

ATOM 2449 CEl HIS B 34 70.689 -8.360 21.808 1.00 44.28 6

ATOM 2450 NE2 HIS B 34 71.323 -7.840 20.763 1.00 44.67 7

ATOM 2451 N ASP B 35 70.439 -12.874 22.263 1.00 36.30 7

ATOM 2452 CA ASP B 35 69.531 -13.176 23.352 1.00 38.71 6

ATOM 2453 C ASP B 35 68.539 -12.055 23.649 1.00 38.11 6

ATOM 2454 O ASP B 35 67.448 -12.373 24.116 1.00 38.15 8

ATOM 2455 CB ASP B 35 70.309 -13.480 24.637 1.00 43.89 6

ATOM 2456 CG ASP B 35 71.071 -14.776 24.631 1.00 48.19 6

ATOM 2457 ODl ASP B 35 71.046 -15.496 23.603 1.00 50.75 8

ATOM 2458 OD2 ASP B 35 71.701 -15.074 25.689 1.00 51.91 8

ATOM 2459 N GLY B 36 68.919 -10.788 23.499 1.00 35.59 7

ATOM 2460 CA GLY B 36 68.007 -9.688 23.778 1.00 33.96 6

ATOM 2461 C GLY B 36 66.844 -9.774 22.751 1.00 32.11 6

ATOM 2462 O GLY B 36 65.738 -9.524 23.235 1.00 30.98 8

ATOM 2463 N HIS B 37 67.149 -10.177 21.521 1.00 31.48 7

ATOM 2464 CA HIS B 37 66.006 -10.322 20.581 1.00 31.68 6

ATOM 2465 C HIS B 37 65.118 -11.479 20.969 1.00 33.06 6

ATOM 2466 O HIS B 37 63.861 -11.440 20.850 1.00 30.99 8

ATOM 2467 CB HIS B 37 66.507 -10.514 19.175 1.00 31.96 6

ATOM 2468 CG HIS B 37 67.366 -9.425 18.643 ' 1.00 34.37 6

ATOM 2469 ND1 HIS B 37 66.888 -8.299 18.005 1.00 37.43 7

ATOM 2470 CD2 HIS B 37 68.714 -9.330 18.624 1.00 34.96 6

ATOM 2471 CEl HIS B 37 67.890 -7.535 17.580 1.00 35.54 6

ATOM 2472 NE2 HIS B 37 69.003 -8.153 17.962 1.00 39.23 7

ATOM 2473 N MET B 38 65.704 -12.577 21.486 1.00 31.32 7

ATOM 2474 CA MET B 38 64.880 -13.668 22.001 1.00 31.44 6

ATOM 2475 C MET B 38 63.959 -13.252 23.115 1.00 29.66 6

ATOM 2476 0 MET B 38 62.851 -13.809 23.253 1.00 28.40 8

ATOM 2477 CB MET B 38 65.799 -14.827,'¹ J487 1.00 34.21 6

ATOM 2478 CG MET B 38 66.423 -15.620' J.375 1.00 35.15 6

ATOM 2479 SD MET B 38 65.631 -15.970 19.832 1.00 35.12 16

ATOM 2480 CE MET B 38 66.123 -14.628 18.770 1.00 36.33 6

ATOM 2481 N LYS B 39 64.228 -12.300 23.996 1.00 29.09 7

ATOM 2482 CA LYS B 39 63.368 -11.857 25.065 1.00 26.18 6

ATOM 2483 C LYS B 39 62.142 -11.078 24.470 1.00 25.41 6

ATOM 2484 LYS B 39 61.042 -11.228 24.964 1.00 26.08 8 -J en en Cπ Cπ J-- J-» CO CO t t o cπ o Cπ O cπ O Cπ O cπ o Cπ O Cπ

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P_ r9 _ r3 _r3 r3 h9 H r3 r3 r3 H3 r_ _r_ r3 >-3 r3 P3 r3 r3 r3 ^ ^ r3 l-3 r3 r3 3 H >-3 H ^ ogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogogoggogogogogooggooggooggogogoogoggooggogo tO t tO tO M W M t t M M I N- tO tO IO IO t ND [\- M tO tO L\D N- lSD N_ l\_ t N_ M

^^^^^^^σ cτιcncτ σ cncncτιcncncΛ.σ cncnc cncncnσ c cncncn

O O O O O O O CD CD C0 C0 CD MD C0 MD CD CD C0000D CD OT C000 C000 ro ^ .-J -J --4 -4 --J ^ -J .-J --J Cn Cn Cn c^ cn cV7--. C WM O CD CO ^ C^ Cn --. C tO M O CD CX) ^ CT^ C1 -^ CΛ) I M O CD CO ^ cn Ul --. C D M O CD OT oaoooooooaooooπoooaoooonoaooooaoooooooaπoooooooooaaooooooπaoc-oooooaooooooa ODOto MMocnto ooto to u- ααcntB N w co α o o to HBD O B > _o α α oo ooto > tO M CO M I M tO M tO M MM tH !w ;> > n O O Ll) O O 00 ^ ^ ^ n_ _ r_O rrj ;> ;> p- P. ω ω ω co ω ω ω t^H l→ l-' i→ L→ lr' ^ ^

G G ^ j i J 'β ^ ^ T- W α σ G G G G α σ α O O O b O e Q Q Q O ^ iτl ^ - ro ^ ^ M M M M M W M W ro ro to to to to to OT to ro ti) D- to t33 to tx) to ro cn cn cn c^ m cΛ n cnc σ^ σ^ c cn o c cn cn cn c cn cy^ cn cn c c σi o^ co co ^ -4 -j -j ^ -j ~j -J cn cn cn cn cn cn cn cn cn c^ cι cjι cn c^ cπ c ι --. -i --. -_. -^ ω ω

-J -J -J -J .-J -J -J -J -J --J -J oι π ώ WΛΛ -> r>ω (- w ! μ w μN>w w co D co ω M M Cjι n cn t co θ M Cjι o M co n cn o o M Cπ cΛ c -^ o CΛj ω π -- ∞ o ro cn .-J

O O CD Cπ M O O CO M ^ ^ -J M Cπ -. CO CO vt* Cπ M M tO Cl CA) Cl Cπ C1 CO fO α-. tO Cn > CO O -^ O CO cn -^ CO C^ o σ^ o ^ co π c co MC ^ co -^ CD --. cn cn M M ^ cj o co -^ co > ^ co -^ M -J t -^ o w cD ^ ^ αi ιt^ co

I I I I I I I I I I

O O --. ω C ) t0 O O M M -^ --. C0 t0 M O O M M Cl J-. M O M t0 ω σi C ) -^ Cπ Cl -J -J -4 -J -J <3^ Cn Cjl O O O M O M - t

^ l\D CA) t CO -^ CD O M CJl O --. O CΛ jl CJ10 D O t -J -^ σ^ σ^ D M C hO C7^ CO -J -J O^ Cπ ^ COCO -J C^ o --. o co ∞ o -J on -^ to ND W cn OT M Cι co ^ co o cΛ> o c^jι ω cA> co o co cπ co ω cji M c M c --J co t^ I n ω ^ co D θ oo co N. M l ^ cD Cπ M -^ o cD θ -J Cπ o c D ^ ^ ι t o -J θ M to oθ M C^ to o ω υι -^ M π -J c -J CD C^

M M M M cπ ϋι co -J oo --J -o on -J Uⁱ to ^[θ --. cπ uι ω ω M θ o W N- M N- --. ιi-. ω -^ π o co c^ μmc_ m μ n Λ^μ ∞m^(_ ∞μ αι MiDM_. M nmm «)ϋi f> tn^N)->MMMu)m nαiN)co∞

-J --. Cπ θ ω M M ^ CJl C0 ^ OT O M -J CΛ tO MD ro θ W Cn ∞ -4 O 00 OT Cπ M t0 C00n CJ1 t0 --J CΛ^} M Cjl O -- O O --. f0 -_. C0 C0 ω M O t0 -^ ^ ^ --. f0 C0 m M C0 M CD C0 t0 --. CJ1 Cn M C0 M O --. CJl M M CD C0 Cn --4 N_ O

'MMMMMMMMMMMMMMMMI 'MMMMMMMMMI ¹ M M M M I ¹ I-* i-r I-* t~* f-* t- f-¹ \ > l-^J l-' t-> -' l-r )-'l-> l-> l-' i-> l-' ->l > >-' -' l-> t-' l-> -r -' ^ t-' l-¹ \

OOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOO OOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOO

--.--. ncπcπCn--^--.Uιcπ-^-^cTicnc πuισϊc cjι nuιcπUιcnc^

01^OTC0αD01^CDCΛ)Cπ MCD-JωCDC0OO-JC0C0CD D^cn0-C)--.--.t0CTi-J iωC0ω cn-4oococnc^cocncj^^cococ onc coσ^cn--Jcncn<D^coo^o -Jc coo^c -JcoOT

ATOM 2707 C LEU B 68 75.575 -2.002 4.715 1.00 46.59 6

ATOM 2708 O LEU B 68 75.241 -3.082 5.201 1.00 47.70 8

ATOM 2709 CB LEU B 68 74.066 -0.198 4.001 1.00 44.25 6

ATOM 2710 CG LEU B 68 72.989 -1.184 3.489 1.00 42.50 6

ATOM 2711 CDl LEU B 68 72.064 -1.563 4.634 1.00 40.69 6

ATOM 2712 CD2 LEU B 68 72.214 -0.620 2.317 1.00 42.43 6

ATOM 2713 N ALA B 69 76.513 -1.866 3.793 1.00 46.99 7

ATOM 2714 CA ALA B 69 77.238 -3.024 3.259 1.00 47.49 6

ATOM 2715 C ALA B 69 77.930 -3.829 4.337 1.00 46.64 6

ATOM 2716 O ALA B 69 77.913 -5.072 4.256 1.00 48.02 8

ATOM 2717 CB ALA B 69 78.258 -2.532 2.235 1.00 48.47 6

ATOM 2718 N ARG B 70 78.475 -3.201 5.370 1.00 45.74 7

ATOM 2719 CA ARG B 70 79.158 -3.961 6.411 1.00 44.24 6

ATOM 2720 C ARG B 70 78.246 -4.487 7.495 1.00 44.00 6

ATOM 2721 O ARG B 70 78.700 -5.308 8.281 1.00 41.15 8

ATOM 2722 CB ARG B 70 80.247 -3.071 7.038 1.00 46.62 6

ATOM 2723 N TYR B 71 76.966 -4.108 7.573 1.00 41.84 7

ATOM 2724 CA TYR B 71 76.076 -4.624 8.609 1.00 39.35 6

ATOM 2725 C TYR B 71 75.935 -6.141 8.508 1.00 37.54 6

ATOM 2726 O TYR B 71 75.788 -6.673 7.410 1.00 37.39 8

ATOM 2727 CB TYR B 71 74.712 -3.919 8.487 1.00 38.73 6

ATOM 2728 CG TYR B 71 73.927 -4.054 9.778 1.00 36.95 6

ATOM 2729 CDl TYR B 71 74.099 -3.155 10.806 1.00 34.97 6

ATOM 2730 CD2 TYR B 71 72.993 -5.079 9.946 1.00 35.71 6

ATOM 2731 CEl TYR B 71 73.405 -3.260 12.004 1.00 35.01 6

ATOM 2732 CE2 TYR B 71 72.287 -5.192 11.109 1.00 33.37 6

ATOM 2733 CZ TYR B 71 72.462 -4.292 12.119 1.00 34.69 6

ATOM 2734 OH TYR B 71 71.765 -4.407 13.290 1.00 34.77 8

ATOM 2735 N PRO B 72 75.985 -6.835 9.625 1.00 37.73 7

ATOM 2736 CA PRO B 72 76.030 -8.293 9.644 1.00 40.09 6

ATOM 2737 C PRO B 72 74.756 -8.966 9.194 1.00 42.74 6

ATOM 2738 O PRO B 72 73.697 -8.753 9.783 1.00 42.94 8

ATOM 2739 CB PRO B 72 76.369 -8.681 11.080 1.00 39.27 6

ATOM 2740 CG PRO B 72 76.366 -7.442 11.876 1.00 39.73 6

ATOM 2741 CD PRO B 72 76.222 -6.266 10.967 1.00 37.89 6

ATOM 2742 N ARG B 73 74.856 -9.773 8.147 1.00 42.53 7

ATOM 2743 CA ARG B 73 73.687 -10.492 7.639 1.00 43.36 6

ATOM 2744 C ARG B 73 73.881 -11.945 7.992 1.00 43.07 6

ATOM 2745 O ARG B 73 74.875 -12.526 7.534 1.00 42.68 8

ATOM 2746 CB ARG B 73 73.524 -10.225 6.143 1.00 45.53 6

ATOM 2747 CG ARG B 73 73.306 -8.700 5.962 1.00 48.13 6

ATOM 2748 CD ARG B 73 72.868 -8.393 4.559 1.00 49.65 6

ATOM 2749 NE ARG B 73 72.537 -7.021 4.268 1.00 51.16 7

ATOM 2750 CZ ARG B 73 73.255 -5.930 4.486 1.00 51.88 6

ATOM 2751 NHl ARG B 73 74.449 -5.968 5.071 1.00 53.24 7

ATOM 2752 NH2 ARG B 73 72.779 -4.755 4.085 1.00 51.96 7

ATOM 2753 N THR B 74 73.054 -12.505 8.869 1.00 40.78 7

ATOM 2754 CA THR B 74 73.184 -13.870 9.338 1.00 38.76 6

ATOM 2755 C THR B 74 71.806 -14.564 9.373 1.00 36.02 6

ATOM 2756 O THR B 74 71.381 -15.074 10.395 1.00 35.74 8

ATOM 2757 CB THR B 74 73.825 -13.949 10.726 1.00 39.81 6

ATOM 2758 OG1 THR B 74 72.965 -13.304 11.686 1.00 41.92 8

ATOM 2759 CG2 THR B 74 75.176 -13.231 10.872 1.00 39.68 6

ATOM 2760 N LEU B 75 71.163 -14.648 8.241 1.00 38.12 7

ATOM 2761 CA LEU B 75 69.795 -15.148 8.140 1.00 38.95 6

ATOM 2762 C LEU B 75 69.657 -16.574 8.644 1.00 39.45 6

ATOM 2763 O LEU B 75 68.791 -16.843 9.478 1.00 37.24 8

ATOM 2764 CB LEU B 75 69.269 -15.024 6.693 1.00 41.95 6

ATOM 2765 CG LEU B 75 67.785 -15.355 6.505 1.00 42.42 6

ATOM 2766 CDl LEU B 75 66.907 -14.527 7.453 1.00 43.76 6

ATOM 2767 CD2 LEU B 75 67.332 -15.146 5.070 1.00 42.41 6

ATOM 2768 N GLN B 76 70.525 -17.509 8.187 1.00 39.28 7

ATOM 2769 CA GLN B 76 70.400 -18.884 8.667 1.00 39.73 6

ATOM 2770 C GLN B 76 70.476 -18.965 10.181 1.00 36.54 6

ATOM 2771 O GLN B 76 69.671 -19.700 10.759 1.00 35.73 8

ATOM 2772 CB GLN B 76 71.477 -19.872 8.150 1.00 42.75 6

ATOM 2773 CG GLN B 76 71.375 -21.209 8.897 1.00 45.19 6

ATOM 2774 CD GLN B 76 72.464 -22.227 8.683 1.00 48.00 6

ATOM 2775 OE1 GLN B 76 72.386 -23.355 9.236 1.00 51.20 8

ATOM 2776 NE2 GLN B 76 73.482 -21.896 7.921 1.00 46.67 7

ATOM 2777 N GLU B 77 71.442 -18.317 10.808 1.00 33.90 7

ATOM 2778 CA GLU B 77 71.585 -18.356 12.259 1.00 33.25 6

ATOM 2779 C GLU B 77 70.408 -17.708 13.013 1.00 32.48 6

ATOM 2780 O GLU B 77 69.960 -18.170 14.072 1.00 31.46 8 ATOM 2781 CB GLU B 77 72.885 -17.636 12.627 1.00 33.79 6 ATOM 2782 N ASP B 78 69.915 -16.625 12.388 1.00 32.55 7 ATOM 2783 CA ASP B 78 68.738 -15.937 12.973 1.00 30.24 6 ATOM 2784 C ASP B 78 67.576 -16.964 12.993 1.00 28.55 6 ATOM 2785 0 ASP B 78 66.981 -17.174 14.032 1.00 29.32 8 ATOM 2786 CB ASP B 78 68.337 -14.697 12.209 1.00 31.08 6 ATOM 2787 CG ASP B 78 69.331 -13.551 12.195 1.00 34.64 6

ATOM 2788 ODl ASP B 78 70.144 -13.494 13.151 1.00 37.80 8

ATOM 2789 OD2 ASP B 78 69.328 -12.744 11.228 1.00 36.82 8

ATOM 2790 N CYS B 79 67.355 -17.543 11.825 1.00 30.19 7

ATOM 2791 CA CYS B 79 66.231 -18.500 11.625 1.00 33.57 6

ATOM 2792 C CYS B 79 66.327 -19.720 12.495 1.00 35.51 6

ATOM 2793 O CYS B 79 65.350 -20.136 13.149 1.00 34.66 8

ATOM 2794 CB CYS B 79 66.184 -18.792 10.132 1.00 33.80 6

ATOM 2795 SG CYS B 79 65.381 -17.456 9.190 1.00 37.92 16

ATOM 2796 N GLU B 80 67.543 -20.281 12.707 1.00 36.68 7

ATOM 2797 CA GLU B 80 67.692 -21.347 13.691 1.00 35.97 6

ATOM 2798 C GLU B 80 67.370 -20.883 15.088 1.00 33.68 6

ATOM 2799 O GLU B 80 66.764 -21.625 15.883 1.00 34.88 8

ATOM 2800 CB GLU B 80 69.130 -21.906 13.660 1.00 36.66 6

ATOM 2801 N LYS B 81 67.668 -19.638 15.520 1.00 34.02 7

ATOM 2802 CA LYS B 81 67.277 -19.253 16.875 1.00 31.36 6

ATOM 2803 C LYS B 81 65.756 -19.047 17.017 1.00 30.38 6

ATOM 2804 O LYS B 81 65.183 -19.326 18.068 1.00 29.64 8

ATOM 2805 CB LYS B 81 67.967 -17.965 17.314 1.00 35.26 6

ATOM 2806 CG LYS B 81 69.451 -18.114 17.566 1.00 37.30 6

ATOM 2807 CD LYS B 81 70.118 -16.744 17.730 1.00 39.14 6

ATOM 2808 CE LYS B 81 71.635 -17.011 17.782 1.00 41.26 6

ATOM 2809 NZ LYS B 81 72.310 -15.733 18.142 1.00 43.00 7

ATOM 2810 N LEU B 82 65.158 -18.495 15.965 1.00 30.34 7

ATOM 2811 CA LEU B 82 63.700 -18.248 16.019 1.00 30.06 6

ATOM 2812 C LEU B 82 62.914 -19.540 16.028 1.00 32.53 6

ATOM 2813 O LEU B 82 61.880 -19.695 16.694 1.00 32.69 8

ATOM 2814 CB LEU B 82 63.335 -17.328 14.845 1.00 30.48 6

ATOM 2815 CG LEU B 82 63.981 -15.924 14.936 1.00 28.69 6

ATOM 2816 CDl LEU B 82 63.820 -15.222 13.603 1.00 25.14 6

ATOM 2817 CD2 LEU B 82 63.412 -15.105 16.103 1.00 28.77 6

ATOM 2818 N ASN B 83 63.438 -20.549 15.323 1.00 33.22 7

ATOM 2819 CA ASN B 83 62.748 -21.849 15.282 1.00 36.28 6

ATOM 2820 C ASN B 83 62.747 -22.507 16.648 1.00 36.28 6

ATOM 2821 O ASN B 83 61.735 -23.043 17.139 1.00 35.49 8

ATOM 2822 CB ASN B 83 63.419 -22.656 14.181 1.00 39.05 6

ATOM 2823 CG ASN B 83 62.717 -23.983 13.943 1.00 42.41 6

ATOM 2824 ODl ASN B 83 63.382 -25.000 14.194 1.00 45.42 8

ATOM 2825 ND2 ASN B 83 61.474 -23.962 13.533 1.00 41.68 7

ATOM 2826 N LYS B 84 63.820 -22.351 17.437 1.00 37.37 7

ATOM 2827 CA LYS B 84 63.850 -22.927 18.780 1.00 39.89 6

ATOM 2828 C LYS B 84 62.942 -22.200 19.747 1.00 40.11 6

ATOM 2829 O LYS B 84 62.533 -22.693 20.801 1.00 40.80 8

ATOM 2830 CB LYS B 84 65.305 -22.932 19.291 1.00 39.81 6

ATOM 2831 N ARG B 85 62.590 -20.942 19.425 1.00 40.09 7

ATOM 2832 CA ARG B 85 61.718 -20.125 20.235 1.00 39.63 6

ATOM 2833 C ARG B 85 60.260 -20.305 19.812 1.00 40.59 6

ATOM 2834 O ARG B 85 59.373 -19.647 20.334 1.00 42.54 8

ATOM 2835 CB ARG B 85 62.093 -18.647 20.134 1.00 40.48 6

ATOM 2836 CG ARG B 85 62.052 -17.972 21.510 1.00 41.38 6

ATOM 2837 CD ARG B 85 63.336 -18.317 22.253 1.00 42.99 6

ATOM 2838 NE ARG B 85 63.380 -17.724 23.588 1.00 42.49 7

ATOM 2839 CZ ARG B 85 64.475 -17.764 24.342 1.00 43.47 6

ATOM 2840 NHl ARG B 85 64.483 -17.233 25.553 1.00 42.44 7

ATOM 2841 NH2 ARG B 85 65.570 -18.361 23.872 1.00 44.83 7

ATOM 2842 N LYS B 86 60.041 -21.151 18.827 1.00 39.06 7

ATOM 2843 CA LYS B 86 58.702 -21.492 18.348 1.00 38.48 6

ATOM 2844 C LYS B 86 57.996 -20.296 17.712 1.00 36.35 6

ATOM 2845 O LYS B 86 56.785 -20.127 17.808 1.00 34.81 8

ATOM 2846 CB LYS B 86 57.903 -22.087 19.511 1.00 39.68 6

ATOM 2847 N VAL B 87 58.751 -19.515 16.953 1.00 33.22 7

ATOM 2848 CA VAL B 87 58.133 -18.416 16.204 1.00 29.42 6

ATOM 2849 C VAL B 87 57.340 -18.986 15.051 1.00 30.11 6

ATOM 2850 O VAL B 87 57.704 -19.959 14.359 1.00 29.33 8

ATOM 2851 CB VAL B 87 59.267 -17.508 15.732 1.00 27.19 6

ATOM 2852 CGI VAL B 87 58.859 -16.637 14.581 1.00 28.11 6

ATOM 2853 CG2 VAL B 87 59.756 -16.644 16.909 1.00 28.45 6

ATOM 2854 N ASP B 88 56.179 -18.408 14.740 1.00 27.32 7 ATOM 2855 CA ASP B 88 55.356 -18.963 13.667 1.00 26.78 6

ATOM 2856 C ASP B 88 55.780 ^■ -18.589 12.285 1.00 26.80 6

ATOM 2857 O ASP B 88 55.687 -19.415 11.342 1.00 26.44 8

ATOM 2858 CB ASP B 88 53.895 -18.488 13.889 1.00 29.04 6

ATOM 2859 CG ASP B 88 53.482 -18.856 15.298 1.00 30.71 6

ATOM 2860 ODl ASP B 88 52.991 -20.020 15.427 1.00 32.60 8

ATOM 2861 OD2 ASP B 88 53.717 -18.147 16.323 1.00 30.59 8

ATOM 2862 N LEU B 89 56.204 -17.356 12.062 1.00 23.49 7

ATOM 2863 CA LEU B 89 56.498 -16.854 10.756 1.00 23.51 6

ATOM 2864 C LEU B 89 57.676 -15.880 10.729 1.00 23.91 6

ATOM 2865 O LEU B 89 57.609 -14.975 11.552 1.00 24.58 8

ATOM 2866 CB LEU B 89 55.236 -16.101 10.292 1.00 26.12 6

ATOM 2867 CG LEU B 89 55.179 -15.845 8.823 1.00 29.47 6

ATOM 2868 CDl LEU B 89 53.725 -15.783 8.333 1.00 31.30 6

ATOM 2869 CD2 LEU B 89 55.883 -14.542 8.494 1.00 32.84 6

ATOM 2870 N VAL B 90 58.629 -15.971 9.842 1.00 23.43 7

ATOM 2871 CA VAL B 90 59.716 -15.006 9.714 1.00 23.35 6

ATOM 2872 C VAL B 90 59.553 -14.315 8.413 1.00 24.66 6

ATOM 2873 O VAL B 90 59.386 -14.905 7.324 1.00 24.98 8

ATOM 2874 CB VAL B 90 61.116 -15.722 9.862 1.00 23.84 6

ATOM 2875 CGI VAL B 90 62.212 -14.701 9.640 1.00 26.41 6

ATOM 2876 CG2 VAL B 90 61.195 -16.379 11.217 1.00 23.75 6

ATOM 2877 N PHE B 91 59.462 -12.972 8.351 1.00 23.00 7

ATOM 2878 CA PHE B 91 59.363 -12.240 7.147 1.00 21.82 6

ATOM 2879 C PHE B 91 60.754 -11.693 6.787 1.00 24.30 6

ATOM 2880 O PHE B 91 61.258 -10.892 7.578 1.00 25.55 8

ATOM 2881 CB PHE B 91 58.346 -11.073 7.207 1.00 20.44 6

ATOM 2882 CG PHE B 91 58.180 -10.275 5.969 1.00 22.85 6

ATOM 2883 CDl PHE B 91 58.030 -10.779 4.676 1.00 21.26 6

ATOM 2884 CD2 PHE B 91 58.164 -8.848 6.101 1.00 22.68 6

ATOM 2885 CEl PHE B 91 57.900 -9.976 3.571 1.00 22.13 6

ATOM 2886 CE2 PHE B 91 58.006 -8.055 4.990 1.00 21.70 6

ATOM 2887 CZ PHE B 91 57.852 -8.587 3.703 1.00 23.17 6

ATOM 2888 N ALA B 92 61.345 -12.164 5.695 1.00 24.62 7

ATOM 2889 CA ALA B 92 62.738 -11.659 5.375 1.00 23.61 6

ATOM 2890 C ALA B 92 62.815 -11.216 3.975 1.00 25.99 6

ATOM 2891 O ALA B 92 63.216 -12.052 3.123 1.00 27.84 8

ATOM 2892 CB ALA B 92 63.656 -12.811 5.743 1.00 25.77 6

ATOM 2893 N PRO B 93 62.300 -10.088 3.518 1.00 25.21 7

ATOM 2894 CA PRO B 93 62.258 -9.655 2.170 1.00 26.28 6

ATOM 2895 C PRO B 93 63.583 -9.189 • 1.617 1.00 25.56 6

ATOM 2896 O PRO B 93 64.455 -8.761 2.381 1.00 27.95 8

ATOM 2897 CB PRO B 93 61.283 -8.471 2.238 1.00 26.93 6

ATOM 2898 CG PRO B 93 61.547 -7.888 3.586 1.00 26.11 6

ATOM 2899 CD PRO B 93 61.769 -9.060 4.516 1.00 24.38 6

ATOM 2900 N SER B 94 63.668 -9.114 0.292 1.00 28.86 7

ATOM 2901 CA SER B 94 64.891 -8.524 -0.309 1.00 30.21 6

ATOM 2902 C SER B 94 64.735 -7.010 -0.305 1.00 31.63 6

ATOM 2903 O SER B 94 63.635 -6.521 -0.100 1.00 27.09 8

ATOM 2904 CB SER B 94 65.138 -8.951 -1.719 1.00 28.52 6

ATOM 2905 OG SER B 94 64.254 -8.353 -2.673 1.00 29.83 8

ATOM 2906 N VAL B 95 65.802 -6.264 -0.628 1.00 32.49 7

ATOM 2907 CA VAL B 95 65.724 -4.840 -0.723 1.00 31.55 6

ATOM 2908 C VAL B 95 64.919 -4.487 -1.938 1.00 31.75 6

ATOM 2909 O VAL B 95 64.138 -3.540 -1.883 1.00 31.41 8

ATOM 2910 CB VAL B 95 67.144 -4.172 -0.780 1.00 32.74 6

ATOM 2911 CGI VAL B 95 67.050 -2.736 -1.221 1.00 34.17 6

ATOM 2912 CG2 VAL B 95 67.813 -4.258 0.570 1.00 33.43 6

ATOM 2913 N LYS B 96 65.004 -5.262 -3.023 1.00 31.26 7

ATOM 2914 CA LYS B 96 64.226 -5.022 -4.212 1.00 31.62 6

ATOM 2915 C LYS B 96 62.744 -5.267 -3.889 1.00 29.22 6

ATOM 2916 O LYS B 96 61.905 -4.611 -4.487 1.00 32.48 8

ATOM 2917 CB LYS B 96 64.685 -5.913 -5.380 1.00 32.35 6

ATOM 2918 N GLU B 97 62.464 -6.172 -2.988 1.00 30.27 7

ATOM 2919 CA GLU B 97 61.056 -6.463 -2.667 1.00 31.03 6

ATOM 2920 C GLU B 97 60.375 -5.301 -1.936 1.00 30.11 6

ATOM 2921 O GLU B 97 59.235 -4.950 -2.211 1.00 31.04 8

ATOM 2922 CB GLU B 97 61.000 -7.749 -1.850 1.00 32.49 6

ATOM 2923 CG GLU B 97 59.570 -8.220 -1.623 1.00 33.54 6

ATOM 2924 CD GLU B 97 58.875 -8.792 -2.844 1.00 35.26 6

ATOM 2925 OE1 GLU B 97 59.540 -9.132 -3.867 1.00 34.07 8

ATOM 2926 OE2 GLU B 97 57.632 -8.980 -2.841 1.00 32.87 8

ATOM 2927 N ILE B 98 61.084 -4.723 -0.999 1.00 28.92 7

ATOM 2928 CA ILE B 98 60.582 -3.564 -0.235 1.00 28.98 6

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ATOM 3003 CA TYR B 108 58.037 8.298 3.677 1.00 22.80 6

ATOM 3004 C TYR B 108 57. 170 8. 870 4. 799 1. 00 23. 19 6

ATOM 3005 O TYR B 108 56. 257 9. 711 4. 564 1. 00 20. 67 8

ATOM 3006 CB TYR B 108 59. 500 8. 861 3. 752 1. 00 26. 29 6

ATOM 3007 CG TYR B 108 59. 581 10. 367 3. 586 1. 00 27. 43 6

ATOM 3008 CDl TYR B 108 59. 350 11. 243 4. 641 1. 00 30. 64 6

ATOM 3009 CD2 TYR B 108 59. 795 10. 914 2. 331 1. 00 31. 95 6

ATOM 3010 CEl TYR B 108 59. 352 12. 617 4. 478 1. 00 31. 91 6

ATOM 3011 CE2 TYR B 108 59. 821 12. 272 2. 159 1. 00 34. 14 6

ATOM 3012 CZ TYR B 108 59. 609 13. 130 3. 235 1. 00 34. 42 6

ATOM 3013 OH TYR B 108 59. 634 14. 497 3. 014 1. 00 36. 77 8

ATOM 3014 N VAL B 109 57. 454 8. 419 6. 031 1. 00 21. 49 7

ATOM 3015 CA VAL B 109 56. 734 8. 809 7. 224 1. 00 21. 55 6

ATOM 3016 C VAL B 109 57. 707 9. 552 8. 149 1. 00 23. 45 6

ATOM 3017 O VAL B 109 58. 712 8. 918 8. 447 1. 00 22. 21 8

ATOM 3018 CB VAL B 109 56. 125 7. 624 8. 009 1. 00 20. 74 6

ATOM 3019 CGI VAL B 109 55. 351 8. 074 9. 216 1. 00 22. 40 6

ATOM 3020 CG2 VAL B 109 55. ,248 6. 829 7. 006 1. 00 21. ,59 6

ATOM 3021 N ASP B 110 57. 376 10. 750 8. 596 1. 00 22. 01 7

ATOM 3022 CA ASP B 110 58. ,343 11. 465 9. 478 1. 00 24. ,43 6

ATOM 3023 C ASP B 110 57. 632 11. 952 10. 711 1. 00 23. 59 6

ATOM 3024 O ASP B 110 56. ,504 12. 458 10. 672 1. 00 21. ,44 8

ATOM 3025 CB ASP B 110 58. ,991 12. 648 8. 759 1. 00 27. ,76 6

ATOM 3026 CG ASP B 110 60. .461 12. .751 9. .239 1. 00 36. ,19 6

ATOM 3027 ODl ASP B 110 61. .056 12. 013 10. 077 1. 00 37. ,59 8

ATOM 3028 OD2 ASP B 110 61. .173 13. 585 8. ,645 1. 00 39. ,38 8

ATOM 3029 N VAL B 111 58. ,257 11. 795 11. 892 1. 00 23. ,56 7

ATOM 3030 CA VAL B 111 57. ,669 12. 175 13. .148 1. 00 22. ,23 6

ATOM 3031 C VAL B 111 58. .397 13. .444 13. .636 1. ,00 26, .13 6

ATOM 3032 O VAL B 111 59. .555 13. ,322 13. ,987 1. ,00 27. .27 8

ATOM 3033 CB VAL B 111 57. .822 11. ,100 14. ,216 1. ,00 23, .73 6

ATOM 3034 CGI VAL B 111 57, .213 11. .440 15, .574 1. .00 23, .64 6

ATOM 3035 CG2 VAL B 111 57. .143 9. ,759 13. .858 1. .00 24. .27 6

ATOM 3036 N PRO B 112 57. .801 14, ,619 13. .564 1. ,00 24, .70 7

ATOM 3037 CA PRO B 112 58, .542 15. .820 13, .939 1. .00 24, .12 6

ATOM 3038 C PRO B 112 59, .048 15, .823 15. .355 1. .00 25, .44 6

ATOM 3039 O PRO B 112 58, .457 15. .302 16. .281 1. .00 25, .94 8

ATOM 3040 CB PRO B 112 57, .517 16. .950 13, .719 1. ,00 26, .49 6

ATOM 3041 CG PRO B 112 56, .471 16. ,411 12, .776 1. ,00 25, .85 6

ATOM 3042 CD PRO B 112 56, .449 14. .912 13, .005 1. .00 25, .31 6

ATOM 3043 N GLY B 113 60 .180 16, .517 15, .580 1, .00 27 .49 7

ATOM 3044 CA GLY B 113 60, .648 16. .709 16, .978 1, .00 27, .16 6

ATOM 3045 C GLY B 113 61. .466 15, .490 17, .404 1, .00 29, .14 6

ATOM 3046 O GLY B 113 62, .690 15. .588 17. .383 1. .00 29, .51 8

ATOM 3047 N LEU B 114 60, .785 14. .355 17, .638 1. .00 27, .78 7

ATOM 3048 CA LEU B 114 61 .512 13, .141 18, .019 1, .00 28 .34 6

ATOM 3049 C LEU B 114 62 .545 12, .685 17 .019 1, .00 29 .38 6

ATOM 3050 O LEU B 114 63 .611 12, .122 17, .362 1, .00 28 .08 8

ATOM 3051 CB LEU B 114 60 .493 12, .006 18 .279 1, .00 26 .74 6

ATOM 3052 CG LEU B 114 59 .539 12, .250 19, .424 1. .00 28 .28 6

ATOM 3053 CDl LEU B 114 58 .565 11, .088 19, .594 1, .00 26 .02 6

ATOM 3054 CD2 LEU B 114 60 .295 12, .476 20 .742 1, .00 28 .90 6

ATOM 3055 N SER B 115 62 .355 12 .921 15 .738 1 .00 28 .55 7

ATOM 3056 CA SER B 115 63 .262 12, .446 1 .710 1, .00 28 .22 6

ATOM 3057 C SER B 115 64 .540 13 .284 14 .611 1. .00 30 .73 6

ATOM 3058 O SER B 115 65 .515 12 .778 14 .048 1 .00 29 .82 8

ATOM 3059 CB SER B 115 62 .556 12 .433 13 .359 1 .00 28 .87 6

ATOM 3060 OG SER B 115 62 .188 13 .728 12 .878 1 .00 31 .15 8

ATOM 3061 N THR B 116 64 .480 14 .501 15 .168 1 .00 30 .45 7

ATOM 3062 CA THR B 116 65 .625 15 .383 14 .934 1 .00 32 .38 6

ATOM 3063 C THR B 116 66 .349 15 .755 16 .226 1 .00 34 .29 6

ATOM 3064 O THR B 116 67 .346 16 .447 16 .085 1 .00 38 .91 8

ATOM 3065 CB THR B 116 65 .213 16 .700 14 .232 1 .00 32 .70 6

ATOM 3066 OG1 THR B 116 64 .062 17 .200 14 .921 1 .00 32 .18 8

ATOM 3067 CG2 THR B 116 64 .868 16 .509 12 .776 1 .00 33 .85 6

ATOM 3068 N MET B 117 65 .882 15 .315 17 .364 1 .00 34 .18 7

ATOM 3069 CA MET B 117 66 .556 15 .577 18 .625 1 .00 35 .31 6

ATOM 3070 C MET B 117 67 .520 14 .454 18 .990 1 .00 37 .27 6

ATOM 3071 O MET B 117 67 .419 13 .329 18 .506 1 .00 35 .45 8

ATOM 3072 CB MET B 117 65 .555 15 .716 19 .758 1 .00 36 .44 6

ATOM 3073 CG MET B 117 64 .825 14 .432 20 .149 1 .00 34 .64 6

ATOM 3074 SD MET B 117 63 .385 14 .720 21 .138 1 .00 35 .68 16

ATOM 3075 CE MET B 117 64 .113 15 .441 22 .628 1 .00 35 .24 6

ATOM 3076 N LEU B 118 68 .432 14 .767 19 .943 1 .00 36 .08 7 ATOM 3077 CA LEU B 118 69.384 13.776 20.444 1.00 35.32 6

ATOM 3078 C LEU B 118 70. 141 13.060 19. 370 1. 00 36. 49 6

ATOM 3079 O LEU B 118 70. 769 13.672 18. 490 1. 00 38. 03 8

ATOM 3080 CB LEU B 118 68. 602 12.780 21. 326 1. 00 34. 52 6

ATOM 3081 CG LEU B 118 67. 955 13.401 22. 550 1. 00 34. 53 6

ATOM 3082 CDl LEU B 118 67. 125 12.422 23. 336 1. 00 33. 90 6

ATOM 3083 CD2 LEU B 118 69. 054 13.987 23. 492 1. 00 36. 09 6

ATOM 3084 N GLU B 119 70. 061 11.719 19. 302 1. 00 39. 19 7

ATOM 3085 CA GLU B 119 70. 748 10.969 18. 252 1. 00 39. 90 6

ATOM 3086 C GLU B 119 70. 345 11.391 16. 861 1. 00 39. 96 6

ATOM 3087 O GLU B 119 71. 144 11.319 15. 930 1. 00 39. 74 8

ATOM 3088 CB GLU B 119 70. 439 9.477 18. 447 1. 00 42. 37 6

ATOM 3089 CG GLU B 119 71. 094 8.560 17. 433 1. 00 46. 28 6

ATOM 3090 CD GLU B 119 70. 981 7.080 17. 777 1. oo - 47. 62 6

ATOM 3091 OE1 GLU B 119 70. 337 6.733 18. 805 1. 00 48. 65 8

ATOM 3092 OE2 GLU B 119 71. 561 6.302 16. 970 1. 00 49. 17 8

ATOM 3093 N GLY B 120 69. 102 11.892 16. 668 1. 00 38. 75 7

ATOM 3094 CA GLY B 120 68. 668 12.258 15. 318 1. 00 39. 65 6

ATOM 3095 C GLY B 120 69. 318 13.524 14. 807 1. 00 41. 25 6

ATOM 3096 O GLY B 120 69. 425 13.755 13. 602 1. 00 39. 83 8

ATOM 3097 N ALA B 121 69. 785 14.354 15. 771 1. 00 42. 58 7

ATOM 3098 CA ALA B 121 70. ,410 15.623 15. ,404 1. 00 44. ,15 6

ATOM 3099 C ALA B 121 71. 647 15.421 14. ,552 1. 00 44. .51 6

ATOM 3100 O ALA B 121 71. ,836 16.162 13. ,587 1. ,00 46. .30 8

ATOM 3101 CB ALA B 121 70. ,755 16.396 16. ,671 1. 00 44. .12 6

ATOM 3102 N SER B 122 72. ,464 14.428 14. ,839 1. ,00 46. ,51 7

ATOM 3103 CA SER B 122 73. ,663 14.179 14. ,040 1. ,00 48. .95 6

ATOM 3104 C SER B 122 73. .442 13.166 12. .932 1. .00 49. .98 6

ATOM 3105 O SER B 122 74. ,351 12.912 12. ,125 1. ,00 49. .74 8

ATOM 3106 CB SER B 122 74. ,790 13.675 14. ,943 1. ,00 49. ,52 6

ATOM 3107 OG SER B 122 74. ,248 12.758 15. ,879 1. 00 51. ,88 8

ATOM 3108 N ARG B 123 72. ,222 12.591 12. ,854 1. ,00 48. ,32 7

ATOM 3109 CA ARG B 123 71. .947 11.586 11. ,826 1. .00 46. .67 6

ATOM 3110 C ARG B 123 70. .694 11.919 11. .018 1. .00 46. .85 6

ATOM 3111 O ARG B 123 69. .644 11.274 11. .155 1. .00 45. .46 8

ATOM 3112 CB ARG B 123 71. .789 10.202 12. .467 1, .00 46. .37 6

ATOM 3113 CG ARG B 123 72. .838 9.776 13. .470 1. .00 46, .42 6

ATOM 3114 CD ARG B 123 72. .773 8.316 13. .871 1. .00 46, .50 6

ATOM 3115 NE ARG B 123 72, .926 7.465 12. .686 1, .00 47. .12 7

ATOM 3116 CZ ARG B 123 72, .709 6.151 12. .722 1. .00 48. .23 6

ATOM 3117 NHl ARG B 123 72, .343 5.594 13, .870 1, .00 48, .08 7

ATOM 3118 NH2 ARG B 123 72 .847 5.460 11, .600 1, .00 48. .83 7

ATOM 3119 N PRO B 124 70 .814 12.888 10 .125 1 .00 46 .75 7

ATOM 3120 CA PRO B 124 69, .724 13.307 9, .272 1, .00 45, .09 6

ATOM 3121 C PRO B 124 69 .159 12.130 8 .501 1 .00 43 .72 6

ATOM 3122 O PRO B 124 69 .907 11.332 7 .919 1 .00 42 .42 8

ATOM 3123 CB PRO B 124 70 .287 14.368 8 .344 1 .00 46 .93 6

ATOM 3124 CG PRO B 124 71 .771 14.278 8 .490 1 .00 47 .37 6

ATOM 3125 CD PRO B 124 72 .023 13.715 9 .861 1 .00 46 .92 6

ATOM 3126 N GLY B 125 67 .828 12.007 8 .537 1 .00 41 .20 7

ATOM 3127 CA GLY B 125 67 .230 10.900 7 .774 1 .00 39 .29 6

ATOM 3128 C GLY B 125 67 .135 9.577 8 .510 1 .00 37 .20 6

ATOM 3129 O GLY B 125 66 .420 8.699 7 .989 1 .00 36 .11 8

ATOM 3130 N HIS B 126 67 .837 9.368 9 .601 1 .00 34 .73 7

ATOM 3131 CA HIS B 126 67 .849 8.102 10 .308 1 .00 33 .50 6

ATOM 3132 C HIS B 126 66 .493 7.708 10 .877 1 .00 32 .20 6

ATOM 3133 O HIS B 126 65 .982 6.611 10 .531 1 .00 31 .89 8

ATOM 3134 CB HIS B 126 68 .894 8.136 11 .442 1 .00 32 .39 6

ATOM 3135 CG HIS B 126 68 .767 6.907 12 .285 1 .00 30 .02 6

ATOM 3136 ND1 HIS B 126 69 .142 5.669 11 .764 1 .00 32 .16 7

ATOM 3137 CD2 HIS B 126 68 .315 6.679 13 .524 1 .00 28 .99 6

ATOM 3138 CEl HIS B 126 68 .928 4.739 12 .670 1 .00 30 .29 6

ATOM 3139 NE2 HIS B 126 68 .411 5.323 13 .726 1 .00 31 .28 7

ATOM 3140 N PHE B 127 65 .874 8.567 11 .680 1 .00 28 .23 7

ATOM 3141 CA PHE B 127 64 .599 8.199 12 .287 1 .00 27 .72 6

ATOM 3142 C PHE B 127 63 .495 8.234 11 .213 1 .00 26 .35 6

ATOM 3143 O PHE B 127 62 .599 7.393 11 .386 1 .00 26 .75 8

ATOM 3144 CB PHE B 127 64 .268 9.034 13 .528 1 .00 27 .25 6

ATOM 3145 CG PHE B 127 65 .109 8.550 14 .698 1 .00 28 .04 6

ATOM 3146 CDl PHE B 127 66 .034 9.472 15 .239 1 .00 27 .72 6

ATOM 3147 CD2 PHE B 127 65 .127 7.278 15 .203 1 .00 26 .78 6

ATOM 3148 CEl PHE B 127 66 .838 9.035 16 .291 1 .00 26 .75 6

ATOM 3149 CE2 PHE B 127 65 .919 6.858 16 .231 1 .00 29 .31 6

ATOM 3150 CZ PHE B 127 66^' .844 7.755 16 .771 1 .00 26 .94 6 ~J en en cπ UI tt-> d-- CO CO M ro h-> o cπ o cπ o l o cπ o UI o Ui o Ui

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ATOM 3299 CB CYS B 147 57.487 -6.803 21.192 1.00 25.97 6

ATOM 3300 SG CYS B 147 56.049 -7.649 21.811 1.00 30.41 16

ATOM 3301 N PHE B 148 59.070 -3.904 21.116 1.00 21.36 7

ATOM 3302 CA PHE B 148 60.268 -3.195 20.823 1.00 19.98 6

ATOM 3303 C PHE B 148 61.134 -3.123 22.146 1.00 19.23 6

ATOM 3304 O PHE B 148 60.479 -3.140 23.148 1.00 23.93 8

ATOM 3305 CB PHE B 148 60.072 -1.760 20.374 1.00 22.31 6

ATOM 3306 CG PHE B 148 59.349 -1.636 19.056 1.00 21.62 6

ATOM 3307 CDl PHE B 148 57.968 -1.677 19.110 1.00 22.35 6

ATOM 3308 CD2 PHE B 148 60.045 -1.548 17.891 1.00 24.41 6

ATOM 3309 CEl PHE B 148 57.226 -1.664 17.918 1.00 21.17 6

ATOM 3310 CE2 PHE B 148 59.307 -1.425 16.674 1.00 23.20 6

ATOM 3311 CZ PHE B 148 57.930 -1.509 16.754 1.00 19.10 6

ATOM 3312 N GLY B 149 62.415 -3.168 22.002 1.00 22.90 7

ATOM 3313 CA GLY B 149 63.243 -3.177 23.235 1.00 24.26 6

ATOM 3314 C GLY B 149 63.315 -1.783 23.884 1.00 26.58 6

ATOM 3315 O GLY B 149 63.397 -0.779 23.199 1.00 27.16 8

ATOM 3316 N GLU B 150 63.380 -1.759 25.212 1.00 27.01 7

ATOM 3317 CA GLU B 150 63.530 -0.425 25.870 1.00 29.68 6

ATOM 3318 C GLU B 150 64.894 0.200 25.737 1.00 31.07 6

ATOM 3319 O GLU B 150 65.020 1.425 25.978 1.00 30.50 8

ATOM - 3320 CB GLU B 150 63.214 -0.532 27.368 1.00 31.68 6

ATOM 3321 CG GLU B 150 61.747 -0.632 27.660 1.00 34.09 6

ATOM 3322 CD GLU B 150 61.359 -0.743 29.111 1.00 37.99 6

ATOM 3323 OE1 GLU B 150 62.205 -0.936 30.001 1.00 38.43 8

ATOM 3324 OE2 GLU B 150 60.143 -0.643 29.350 1.00 40.17 8

ATOM 3325 N LYS B 151 65.951 -0.544 25.401 1.00 29.23 7

ATOM 3326 CA LYS B 151 67.258 0.093 25.292 1.00 31.41 6

ATOM 3327 C LYS B 151 67.273 1.220 24.300 1.00 31.27 6

ATOM 3328 O LYS B 151 67.936 2.260 24.433 1.00 27.21 8

ATOM 3329 CB LYS B 151 68.320 -0.926 24.878 1.00 34.10 6

ATOM 3330 CG LYS B 151 69.755 -0.397 24.923 1.00 37.66 6

ATOM 3331 CD LYS B 151 70.640 -1.476 24.317 1.00 41.05 6

ATOM 3332 CE LYS B 151 72.080 -1.431 24.765 1.00 43.98 6

ATOM 3333 NZ LYS B 151 72.893 -0.452 23.975 1.00 44.59 7

ATOM 3334 N ASP B 152 66.506 1.027 23.164 1.00 28.39 7

ATOM 3335 CA ASP B 152 66.518 2.032 22.110 1.00 28.38 6

ATOM 3336 C ASP B 152 65.332 2.937 22.374 1.00 28.23 6

ATOM 3337 O ASP B 152 64.210 2.803 21.783 1.00 26.26 8

ATOM 3338 CB ASP B 152 66.440 1.375 20.725 1.00 28.61 6

ATOM 3339 N PHE B 153 65.516 3.702 23.467 1.00 25.07 7

ATOM 3340 CA PHE B 153 64.373 4.471 23.974 1.00 26.53 6

ATOM 3341 C PHE B 153 63.892 5.520 22.974 1.00 21.61 6

ATOM 3342 O PHE B 153 62.708 5.839 23.024 1.00 24.77 8

ATOM 3343 CB PHE B 153 64.730 5.118 25.330 1.00 26.51 6

ATOM 3344 CG PHE B 153 65.779 6.167 25.190 1.00 29.71 6

ATOM 3345 CDl PHE B 153 65.443 7.493 24.943 1.00 29.96 6

ATOM 3346 CD2 PHE B 153 67.132 5.855 25.398 1.00 29.77 6

ATOM 3347 CEl PHE B 153 66.423 8.454 24.846 1.00 31.18 6

ATOM 3348 CE2 PHE B 153 68.099 6.820 25.256 1.00 28.84 6

ATOM 3349 CZ PHE B 153 67.763 8.135 24.997 1.00 31.32 6

ATOM 3350 N GLN B 154 64.740 6.002 22.113 1.00 23.01 7

ATOM 3351 CA GLN B 154 64.352 7.012 21.149 1.00 24.58 6

ATOM 3352 C GLN B 154 63.443 6.353 20.075 1.00 24.87 6

ATOM 3353 O GLN B 154 62.466 6.997 19.707 1.00 23.87 8

ATOM 3354 CB GLN B 154 65.558 7.664 20.502 1.00 26.01 6

ATOM 3355 CG GLN B 154 65.117 8.877 19.710 1.00 28.34 6

ATOM 3356 CD GLN B 154 66.171 9.934 19.456 1.00 30.51 6

ATOM 3357 OE1 GLN B 154 67.342 9.742 19.766 1.00 32.27 8

ATOM 3358 NE2 GLN B 154 65.742 11.030 18.839 1.00 28.70 7

ATOM 3359 N GLN B 155 63.841 5.183 19.619 1.00 24.42 7

ATOM 3360 CA GLN B 155 62.944 4.439 18.714 1.00 24.63 6

ATOM 3361 C GLN B 155 61.612 4.204 19.382 1.00 22.70 6

ATOM 3362 O GLN B 155 60.577 4.285 18.652 1.00 24.30 8

ATOM 3363 CB GLN B 155 63.549 3.094 18.268 1.00 25.06 6

ATOM 3364 CG GLN B 155 64.450 3,209 17.029 1.00 29.61 6

ATOM 3365 CD GLN B 155 64.506 1.856 16.285 1.00 32.67 6

ATOM 3366 OE1 GLN B 155 65.360 1.610 15.440 1.00 37.92 8

ATOM 3367 NE2 GLN B 155 63.610 0.953 16.599 1.00 28.61 7

ATOM 3368 N LEU B 156 61.522 3.748 20.602 1.00 20.20 7

ATOM 3369 CA LEU B 156 60.288 3.409 21.273 1.00 22.81 6

ATOM 3370 C LEU B 156 59.381 4.671 21.280 1.00 25.01 6

ATOM 3371 O LEU B 156 58.192 4.596 20.961 1.00 22.03 8

ATOM 3372 CB LEU B 156 60.549 2.887 22.651 1.00 23.28 6 l en σ> Ul αi d-» d-- CO co to CO μ-¹ o cπ o αi o Ul o cπ o cπ o π o π

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ATOM 3521 C PRO B 176 63.888 -4.974 29.180 1.00 32.41 6

ATOM 3522 O PRO B 176 63.831 -6.135 28.746 1.00 28.92 8

ATOM 3523 CB PRO B 176 62.159 -4.588 30.980 1.00 33.03 6

ATOM 3524 CG PRO B 176 60.685 -4.380 30.922 1.00 34.15 6

ATOM 3525 CD PRO B 176 60.320 -4.916 29.543 1.00 28.09 6

ATOM 3526 N ILE B 177 65.121 -4.418 29.353 1.00 31.48 7

ATOM 3527 CA ILE B 177 66.307 -5.079 28.865 1.00 32.30 6

ATOM 3528 C ILE B 177 66.572 -6.407 29.607 1.00 30.07 6

ATOM 3529 O ILE B 177 66.054 -6.698 30.686 1.00 32.04 8

ATOM 3530 CB ILE B 177 67.641 -4.292 28.903 1.00 33.70 6

ATOM 3531 CGI ILE B 177 68.066 -3.943 30.331 1.00 33.12 6

ATOM 3532 CG2 ILE B 177 67.518 -3.039 28.030 1.00 34.28 6

ATOM 3533 CDl ILE B 177 69.430 -3.243 30.349 1.00 34.81 6

ATOM 3534 N MET B 178 67.408 -7.204 28.952 1.00 32.08 7

ATOM 3535 CA MET B 178 67.674 -8.503 29.572 1.00 35.37 6

ATOM 3536 C MET B 178 68.620 -8.292 30.772 1.00 34.12 6

ATOM 3537 O MET B 178 69.597 -7.573 30.642 1.00 31.98 8

ATOM 3538 CB MET B 178 68.295 -9.532 28.641 1.00 40.27 6

ATOM 3539 CG MET B 178 67.437 -10.819 28.679 1.00 44.21 6

ATOM 3540 SD MET B 178 68.203 -12.124 27.749 1.00 51.85 16

ATOM 3541 CE MET B 178 69.561 -11.316 26.916 1.00 48.86 6

ATOM 3542 N ARG B 179 68.313 -8.994 31.814 1.00 35.69 7

ATOM 3543 CA ARG B 179 69.085 -8.847 33.060 1.00 36.43 6

ATOM 3544 C ARG B 179 69.292 -10.188 33.715 1.00 37.86 6

ATOM 3545 O ARG B 179 68.430 -11.054 33.618 1.00 38.23 8

ATOM 3546 CB ARG B 179 68.260 -7.887 33.870 1.00 36.62 6

ATOM 3547 CG ARG B 179 68.473 -7.248 35.163 1.00 38.40 6

ATOM 3548 CD ARG B 179 67.373 -6.311 35.598 1.00 34.70 6

ATOM 3549 NE ARG B 179 67.202 -5.122 34.808 1.00 31.82 7

ATOM 3550 CZ ARG B 179 68.057 -4.149 34.534 1.00 32.71 6

ATOM 3551 NHl ARG B 179 69.308 -4.167 34.984 1.00 30.99 7

ATOM 3552 NH2 ARG B 179 67.715 -3.067 33.831 1.00 33.25 7

ATOM 3553 N ALA B 180 70.363 -10.335 34.477 1.00 36.11 7

ATOM 3554 CA ALA B 180 70.602 -11.562 35.235 1.00 36.60 6

ATOM 3555 C ALA B 180 69.640 -11.614 36.404 1.00 36.37 6

ATOM 3556 O ALA B 180 68.929 -10.685 36.743 1.00 36.44 8

ATOM 3557 CB ALA B 180 72.048 -11.541 35.689 1.00 36.08 6

ATOM 3558 N LYS B 181 69.621 -12.775 37.102 1.00 37.25 7

ATOM 3559 CA LYS B 181 68.797 -12.903 38.292 1.00 38.41 6

ATOM 3560 C LYS B 181 69.223 -11.942 39.395 1.00 37.82 6

ATOM 3561 O LYS B 181 68.366 -11.482 40.158 1.00 40.11 8

ATOM 3562 CB LYS B 181 68.862 -14.317 38.895 1.00 39.54 6

ATOM 3563 N ASP B 182 70.495 -11.584 39.503 1.00 36.65 7

ATOM 3564 CA ASP B 182 70.935 -10.663 40.548 1.00 35.51 6

ATOM 3565 C ASP B 182 70.714 -9.206 40.091 1.00 35.06 6

ATOM 3566 O ASP B 182 71.004 -8.303 40.868 1.00 33.11 8

ATOM 3567 CB ASP B 182 72.392 -10.861 40.981 1.00 37.04 6

ATOM 3568 CG ASP B 182 73.414 -10.661 39.890 1.00 38.43 6

ATOM 3569 ODl ASP B 182 73.047 -10.265 38.753 1.00 38.66 8

ATOM 3570 OD2 ASP B 182 74.624 -10.938 40.116 1.00 38.45 8

ATOM 3571 N GLY B 183 70.283 -8.992 38.840 1.00 35.23 7

ATOM 3572 CA GLY B 183 69.907 -7.618 38.467 1.00 32.81 6

ATOM 3573 C GLY B 183 70.883 -7.003 37.494 1.00 33.61 6

ATOM 3574 O GLY B 183 70.523 -5.956 36.928 1.00 33.06 8

ATOM 3575 N LEU B 184 72.029 -7.592 37.220 1.00 31.99 7

ATOM 3576 CA LEU B 184 72.977 -7.004 36.286 1.00 32.29 6

ATOM 3577 C LEU B 184 72.517 -7.011 34.826 1.00 33.46 6

ATOM 3578 O LEU B 184 72.300 -8.130 34.314 1.00 32.16 8

ATOM 3579 CB LEU B 184 74.325 -7.737 36.370 1.00 32.38 6

ATOM 3580 CG LEU B 184 75.481 -7.019 35.655 1.00 32.34 6

ATOM 3581 CDl LEU B 184 75.643 -5.559 36.125 1.00 34.61 6

ATOM 3582 CD2 LEU B 184 76.748 -7.838 35.853 1.00 34.57 6

ATOM 3583 N ALA B 185 72.466 -5.818 34.204 1.00 32.96 7

ATOM 3584 CA ALA B 185 72.099 -5.821 32.780 1.00 33.17 6

ATOM 3585 C ALA B 185 73.053 -6.670 31.950 1.00 35.69 6

ATOM 3586 O ALA B 185 74.281 -6.510 32.057 1.00 35.57 8

ATOM 3587 CB ALA B 185 72.076 -4.368 32.316 1.00 29.95 6

ATOM 1443 N LEU B 186 72.752 -7.823 31.203 1.00 16.87

ATOM 1444 CA LEU B 186 73.699 -8.676 30.476 1.00 16.99

ATOM 1445 C LEU B 186 74.354 -7.793 29.406 1.00 17.67

ATOM 1446 O LEU B 186 73.662 -7.050 28.666 1.00 20.34

ATOM 1447 CB LEU B 186 73.001 -9.890 29.872 1.00 16.87

ATOM 1448 CG LEU B 186 72.315 -10.841 30.851 1.00 18.67

ATOM 1449 CDl LEU B 186 71.803 -12.062 30.097 1.00 20.67 ATOM 1450 CD2 LEU B 186 73.289 --11.257 31.936 1.00 17.31

ATOM 1451 N SER B 187 75.650 -7.991 29.285 1.00 18. 83

ATOM 1452 CA SER B 187 76.407 -7.179 28.327 1.00 17. 18

ATOM 1453 C SER B 187 77.754 -7.771 28.079 1.00 17. 64

ATOM 1454 O SER B 187 78.405 -8.305 28.987 1.00 18. 63

ATOM 1455 CB SER B 187 76.597 -5.762 28.933 1.00 20. 23

ATOM 1456 OG SER B 187 77.485 -4.989 28.093 1.00 20. 91

ATOM 1457 N SER B 188 78.290 -7.564 26.832 1.00 17. 55

ATOM 1458 CA SER B 188 79.706 -7.917 26.649 1.00 17. 70

ATOM 1459 C SER B 188 80.653 -7.182 27.579 1.00 17. 74

ATOM 1460 O SER B 188 81.764 -7.648 27.944 1.00 18. 92

ATOM 1461 CB SER B 188 80.127 -7.598 25.196 1.00 19. 73

ATOM 1462 OG SER B 188 79.893 -6.208 24.915 1.00 20. 84

ATOM 1463 N ARG B 189 80.298 -6.012 28.096 1.00 18. 16

ATOM 1464 CA ARG B 189 81.104 -5.205 28.988 1.00 19. 85

ATOM 1465 C ARG B 189 81.386 -5.909 30.311 1.00 20. 33

ATOM 1466 O ARG B 189 82.356 -5.612 30.969 1.00 21. 91

ATOM 1467 CB ARG B 189 80.426 -3.848 29.284 1.00 20. 55

ATOM 1468 CG ARG B 189 80.245 -3.075 27.973 1.00 22. 89

ATOM 1469 CD ARG B 189 79.609 -1.707 28.273 1.00 23. 21

ATOM 1470 NE ARG B 189 79.461 -1.073 26.939 1.00 25. 97

ATOM 1471 CZ ARG B 189 " 79.880 0.157 26.683 1.00 28. 29

ATOM 1472 NHl ARG B 189 80.387 0.915 27.617 1.00 26. 60

ATOM 1473 NH2 ARG B 189 79.714 0.627 25.429 1.00 28. 41

ATOM 1474 N ASN B 190 80.441 -6.790 30.763 1.00 19. 42

ATOM 1475 CA ASN B 190 80.639 -7.442 32.041 1.00 19. 64

ATOM 1476 C ASN B 190 81.891 -8.271 32.059 1.00 22. ,61

ATOM 1477 O ASN B 190 82.467 -8.717 33.097 1.00 23. ,27

ATOM 1478 CB ASN B 190 79.437 -8.347 32.355 1.00 19. .54

ATOM 1479 CG ASN B 190 78.168 -7.518 32.494 1.00 21. .41

ATOM 1480 ODl ASN B 190 77.045 -8.077 32.323 1.00 21. ,40

ATOM 1481 ND2 ASN B 190 78.310 -6.244 32.814 1.00 19. ,16

ATOM 1497 N GLY B 191 82.333 -8.712 30.735 1.00 27. .44

ATOM 1498 CA GLY B 191 83.554 -9.514 30.632 1.00 28. .04

ATOM 1499 C GLY B 191 84.823 -8.796 31.035 1.00 29. .70

ATOM 1500 O GLY B 191 85.815 -9.487 31.266 1.00 31. .47

ATOM 1482 N TYR B 192 84.825 -7.501 31.228 1.00 26, .92

ATOM 1483 CA TYR B 192 86.032 -6.786 31.629 1.00 29, .88

ATOM 1484 C TYR B 192 86.054 -6.581 33.125 1.00 29, .91

ATOM 1485 O TYR B 192 87.053 -5.998 33.601 1.00 34, .28

ATOM 1486 CB TYR B 192 86.154 -5.424 30.922 1.00 30, .32

ATOM 1487 CG TYR B 192 86.340 -5.687 29.438 1.00 32, .17

ATOM 1488 CDl TYR B 192 85.211 -5.943 28.667 1.00 32 .38

ATOM 1489 CD2 TYR B 192 87.596 -5.764 28.842 1.00 34, .00

ATOM 1490 CEl TYR B 192 85.313 -6.234 27.337 1.00 35, .21

ATOM 1491 CE2 TYR B 192 87.703 -6.056 27.486 1.00 34, .55

ATOM 1492 CZ TYR B 192 86.578 -6.276 26.747 1.00 36 .66

ATOM 1493 OH TYR B 192 86.631 -6.577 25.395 1.00 38 .33

ATOM 1494 N LEU B 193 85.033 -7.028 33.865 1.00 28 .20

ATOM 1495 CA LEU B 193 85.075 -6.900 35.299 1.00 26 .63

ATOM 1496 C LEU B 193 85.870 -7.994 35.986 1.00 27 .15

ATOM 1497 O LEU B 193 85.690 -9.155 35.614 1.00 28 .28

ATOM 1498 CB LEU B 193 83.651 -6.979 35.888 1.00 26 .20

ATOM 1499 CG LEU B 193 82.648 -5.971 35.339 1.00 25 .58

ATOM 1500 CDl LEU B 193 81.223 -6.375 35.649 1.00 24 .08

ATOM 1501 CD2 LEU B 193 82.909 -4.563 35.910 1.00 27 .77

ATOM 1502 N THR B 194 86.596 -7.704 37.090 1.00 28 .42

ATOM 1503 CA THR B 194 87.177 -8.819 37.838 1.00 27 .62

ATOM 1504 C THR B 194 86.087 -9.564 38.585 1.00 25 .74

ATOM 1505 O THR B 194 84.983 -8.990 38.712 1.00 26 .48

ATOM 1506 CB THR B 194 88.236 -8.313 38.835 1.00 29 .34

ATOM 1507 OG1 THR B 194 87.611 -7.354 39.693 1.00 30 .55

ATOM 1508 CG2 THR B 194 89.370 -7.647 38.064 1.00 32 .65

ATOM 3620 N ALA B 195 86.095 -11.397 38.739 1.00 45 .01 7

ATOM 3621 CA ALA B 195 85.137 -12.052 39.619 1.00 45 .61 6

ATOM 3622 C ALA B 195 84.702 -11.095 40.732 1.00 46 .90 6

ATOM 3623 O ALA B 195 83.510 -11.093 41.082 1.00 45 .91 8

ATOM 3624 CB ALA B 195 85.717 -13.336 40.196 1.00 46 .79 6

ATOM 3625 N GLU B 196 85.603 -10.280 41.278 1.00 47 .33 7

ATOM 3626 CA GLU B 196 85.242 -9.350 42.330 1.00 48 .34 6

ATOM 3627 C GLU B 196 84.313 -8.252 41.828 1.00 46 .99 6

ATOM 3628 O GLU B 196 83.325 -7.912 42.497 1.00 47 .72 8

ATOM 3629 CB GLU B 196 86.459 -8.634 42.959 1.00 52 .20 6

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ATOM 4149 O VAL B 265 74.044 3.750 32.557 1.00 34.46 8

ATOM 4150 CB VAL B 265 72. 642 4.856 35. 202 1.00 32. 74 6

ATOM 4151 CGI VAL B 265 71. 525 5.474 36. 025 1.00 33. 45 6

ATOM 4152 CG2 VAL B 265 72. 331 3.361 35. 046 1.00 33. 30 6

ATOM 4153 N ALA B 266 75. 219 5.485 33. 397 1.00 33. 41 7

ATOM 4154 CA ALA B 266 76. 501 4.926 33. 000 1.00 32. 14 6

ATOM 4155 C ALA B 266 77. 411 5.092 34. 221 1.00 32. 17 6

ATOM 4156 O ALA B 266 77. 390 6.213 34. 746 1.00 32. 13 8

ATOM 4157 CB ALA B 266 77. 139 5.570 31. 794 1.00 32. 99 6 0 ATOM 4158 N ALA B 267 78. 175 4.058 34. 569 1.00 31. 42 7

ATOM 4159 CA ALA B 267 79. 107 4.338 35. 679 1.00 32. 75 6

ATOM 4160 C ALA B 267 80. 356 3.503 35. 491 1.00 35. 34 6

ATOM 4161 O ALA B 267 80. 213 2.423 34. 884 1.00 36. 90 8

ATOM 4162 CB ALA B 267 78. 446 4.006 36. 993 1.00 31. 22 6 5 ATOM 4163 N TRP B 268 81. 511 3.868 36. 036 1.00 36. 69 7

ATOM 4164 CA TRP B 268 82. 665 2.974 35. 881 1.00 38. 65 6

ATOM 4165 C TRP B 268 82. 910 2.113 37. 105 1.00 40. 28 6

ATOM 4166 O TRP B 268 82. 777 2.579 38. 235 1.00 38. 57 8

ATOM 4167 CB TRP B 268 83. 927 3.805 35. 609 1.00 40. 65 6 0 ATOM 4168 CG TRP B 268 83. 860 4.563 34. 319 1.00 43. 80 6

ATOM 4169 CDl TRP B 268 83. 114 5.662 34. 040 1.00 44. 47 6

ATOM 4170 CD2 TRP B 268 84. 577 4.256 33. 115 1.00 45. 14 6

ATOM 4171 NE1 TRP B 268 83. 311 6.063 32. ,729 1.00 45. ,41 7

ATOM 4172 CE2 TRP B 268 84. 199 5.211 32. ,144 1.00 45. ,95 6

25 ATOM 4173 CE3 TRP B 268 85. ,470 3.244 32. ,757 1.00 45. .65 6

ATOM 4174 CZ2 TRP B 268 84. 703 5.199 30. ,836 1.00 46. .17 6

ATOM 4175 CZ3 TRP B 268 85. 984 3.242 31. ,463 1.00 46. ,00 6

ATOM 4176 CH2 TRP B 268 85. ,596 4.206 30. ,522 1.00 45. .63 6

ATOM 4177 N LEU B 269 83. 300 0.869 36. ,821 1.00 39. ,18 7

30 ATOM 4178 CA LEU B 269 83. ,691 -0.026 37. .916 1.00 43. ,86 6

ATOM 4179 C LEU B 269 85. .093 -0.471 37. .522 1.00 46. .33 6

ATOM 4180 O LEU B 269 85. ,247 -0.946 36, .400 1.00 47, .07 8

ATOM 4181 CB LEU B 269 82. .635 -1.086 38, .058 1.00 43. .77 6

ATOM 4182 CG LEU B 269 82. .651 -2.072 39, .212 1.00 44. .62 6

35 ATOM 4183 CDl LEU B 269 82. .571 -1.312 40, .537 1.00 44. .46 6

ATOM 4184 CD2 LEU B 269 81. .518 -3.080 39, .046 1.00 42. .39 6

ATOM 4185 N GLY B 270 86. ,102 -0.049 38, .293 1.00 48. .41 7

ATOM 4186 CA GLY B 270 87. .475 -0.340 37. .862 1.00 51. .49 6

ATOM 4187 C GLY B 270 87. .681 0.391 36 .532 1.00 54, .10 6

A Q ATOM 4188 O GLY B 270 87. .397 1.588 36, .464 1.00 54, .18 8

ATOM 4189 N ASP B 271 88. .108 -0.331 35 .503 1.00 56, .24 7

ATOM 4190 CA ASP B 271 88, .288 0.320 34 .199 1.00 56, .89 6

ATOM 4191 C ASP B 271 87 .142 -0.096 33 .280 1.00 54 .99 6

ATOM 4192 O ASP B 271 87 .162 0.231 32 .097 1.00 55 .57 8

45 ATOM 4193 CB ASP B 271 89, .670 0.026 33 .618 1.00 60 .69 6

ATOM 4194 CG ASP B 271 90, .400 -1.175 34 .164 1.00 64 .16 6

ATOM 4195 ODl ASP B 271 89 .789 -2.194 34 .571 1.00 65 .71 8

ATOM 4196 OD2 ASP B 271 91 .657 -1.179 34 .206 1.00 66 .40 8

ATOM 4197 N ALA B 272 86 .129 -0.780 33 .807 1.00 52 .97 7

50 ATOM 4198 CA ALA B 272 84 .966 -1.186 33 .031 1.00 50 .67 6

ATOM 4199 C ALA B 272 83 .843 -0.149 33 .103 1.00 50 .64 6

ATOM 4200 O ALA B 272 83 .482 0.315 34 .203 1.00 49 .32 8

ATOM 4201 CB ALA B 272 84 .389 -2.501 33 .520 1.00 50 .42 6

ATOM 4202 N ARG B 273 83 .255 0.166 31 .958 1.00 47 .60 7

55 ATOM 4203 CA ARG B 273 82 .163 1.131 31 .939 1.00 46 .77 6

ATOM 4204 C ARG B 273 80 .841 0.398 31 .804 1.00 45 .84 6

ATOM 4205 O ARG B 273 80 .636 -0.256 30 .770 1.00 46 .17 8

ATOM 4206 CB ARG B 273 82 .312 2.144 30 .804 1.00 48 .87 6

ATOM 4207 CG ARG B 273 81 .234 3.214 30 .839 1.00 49 .86 6

60 ATOM 4208 CD ARG B 273 81 .436 4.283 29 .773 1.00 52 .81 6

ATOM 4209 NE ARG B 273 80 .277 5.174 29 .733 1.00 54 .38 7

ATOM 4210 CZ ARG B 273 79 .665 5.669 28 .671 1.00 55 .34 6

ATOM 4211 NHl ARG B 273 80 .083 5.410 27 .433 1.00 56 .45 7

ATOM 4212 NH2 ARG B 273 78 .606 6.455 28 .819 1.00 54 .66 7

65 ATOM 4213 N LEU B 274 79 .992 0.448 32 .821 1.00 41 .38 7

ATOM 4214 CA LEU B 274 78 .715 -0.229 32 .792 1.00 37 .98 6

ATOM 4215 C LEU B 274 77 .584 0.737 32 .506 1.00 37 .26 6

ATOM 4216 O LEU B 274 77 .586 1.908 32 .909 1.00 36 .11 8

ATOM 4217 CB LEU B 274 78 .395 -0.939 34 .118 1.00 38 .68 6

70 ATOM 4218 CG LEU B 274 79 .554 -1.797 34 .654 1.00 41 .26 6

ATOM 4219 CDl LEU B 274 79 .161 -2.469 35 .960 1.00 41 .73 6

ATOM 4220 CD2 LEU B 274 79 .999 -2.827 33 .625 1.00 42 .85 6

ATOM 4221 N ILE B 275 76 .603 0.270 31 .724 1.00 35 .74 7

ATOM 4222 CA ILE B 275 75 .493 1.141 31 .372 1.00 33 .53 6 ATOM 4223 C ILE B 275 74.202 0.402 31.685 1.00 32.45 6

ATOM 4224 O ILE B 275 74. 121 -0.836 31. 733 1. 00 31. 50 8

ATOM 4225 CB ILE B 275 75. 466 1.658 29. 914 1. 00 36. 92 6

ATOM 4226 CGI ILE B 275 75. 105 0.527 28. 946 1. 00 37. 93 6

ATOM 4227 CG2 ILE B 275 76. 794 2.331 29. 537 1. 00 36. 91 6

ATOM 4228 CDl ILE B 275 74. 962 1.004 27. 506 1. 00 38. 53 6

ATOM 4229 N ASP B 276 73. 124 1.174 31. 933 1. 00 28. 46 7

ATOM 4230 CA ASP B 276 71. 866 0.517 32. 262 1. 00 30. 30 6

ATOM 4231 C ASP B 276 70. 716 1.517 32. 068 1. 00 29. 63 6

ATOM 4232 O ASP B 276 71. 081 2.666 31. 835 1. 00 27. 88 8

ATOM 4233 CB ASP B 276 71. 937 -0.066 33. 671 1. 00 32. 97 6

ATOM 4234 CG ASP B 276 70. 851 -1.058 33. 987 1. 00 34. 63 6

ATOM 4235 ODl ASP B 276 69. 857 -1.272 33. 231 1. 00 37. 08 8

ATOM 4236 OD2 ASP B 276 70. 931 -1.716 35. 054 1. 00 35. 37 8

ATOM 4237 N ASN B 277 69. 478 1.072 32. 012 1. 00 30. 76 7

ATOM 4238 CA ASN B 277 68. 339 1.963 31. 738 1. 00 31. 92 6

ATOM 4239 C ASN B 277 67. 121 1.388 32. ,426 1. 00 29. 27 6

ATOM 4240 O ASN B 277 67. 035 0.187 32. 641 1. 00 30. 64 8

ATOM 4241 CB ASN B 277 68. 041 2.214 30. 258 1. 00 37. 99 6

ATOM 4242 CG ASN B 277 66. 700 1.999 29. 601 1. 00 41. 20 6

ATOM 4243 ODl ASN B 277 65. 702 1.397 30. ,046 1. ,00 41. ,98 8

ATOM 4244 ND2 ASN B 277 66. 503 2.495 28. ,345 1. ,00 41. ,86 7

ATOM 4245 N LYS B 278 66. ,149 2.219 32. ,760 1. .00 28. .29 7

ATOM 4246 CA LYS B 278 64. ,891 1.736 33. .328 1. .00 30. .58 6

ATOM 4247 C LYS B 278 63. ,822 2.756 32. .929 1. .00 33. ,32 6

ATOM 4248 O LYS B 278 64. ,130 3.940 32. .793 1. . 00 32. .01 8

ATOM 4249 CB LYS B 278 64. ,919 1.486 34. .834 1. ,00 31. ,32 6

ATOM 4250 CG LYS B 278 63. .617 0.953 35. .422 1. .00 35. ,08 6

ATOM 4251 CD LYS B 278 63. ,793 0.340 36. .790 1. .00 38. .13 6

ATOM 4252 CE LYS B 278 63. ,031 -0.950 37. .108 1. .00 39. .29 6

ATOM 4253 NZ LYS B 278 63. .193 -1.103 38, .612 1. .00 44. .44 7

ATOM 4254 N MET B 279 62. ,625 2.256 32, .594 1. . 00 33. .66 7

ATOM 4255 CA MET B 279 61. .488 3.102 32, .303 1, .00 36, .39 6

ATOM 4256 C MET B 279 60, .543 3.014 33, .483 1, .00 35, .26 6

ATOM 4257 O MET B 279 60, ,470 1.929 34, .090 1, .00 38, .21 8

ATOM 4258 CB MET B 279 60. .797 2.708 30, .965 1, .00 38, .06 6

ATOM 4259 CG MET B 279 61, .358 3.604 29 .846 1 .00 42 .01 6

ATOM 4260 SD MET B 279 61. .219 2.888 28 .222 1. .00 48, .77 16

ATOM 4261 CE MET B 279 62, .632 3.595 27, .392 1 .00 46, .06 6

ATOM 4262 N VAL B 280 59, .853 4.082 33 .859 1. .00 34 .69 7

ATOM 4263 CA VAL B 280 58, .937 4.046 34 .991 1, .00 37 .86 6

ATOM 4264 C VAL B 280 57 .655 4.778 34 .624 1 .00 39 .91 6

ATOM 4265 O VAL B 280 57, .722 5.842 33 .971 1 .00 39 .57 8

ATOM 4266 CB VAL B 280 59, .605 4.627 36 .262 1 .00 40 .03 6

ATOM 4267 CGI VAL B 280 60 .582 5.734 35 .894 1 .00 40 .43 6

ATOM 4268 CG2 VAL B 280 58 .595 5.132 37 .286 1 .00 41 .28 6

ATOM 4269 N GLU B 281 56 .521 4.221 35 .046 1 .00 42 .47 7

ATOM 4270 CA GLU B 281 55 .243 4.911 34 .809 1 .00 45 .74 6

ATOM 4271 C GLU B 281 54 .973 5.919 35 .910 1 . 00 47 .07 6

ATOM 4272 O GLU B 281 55 .370 5.595 37 .039 1 .00 46 .25 8

ATOM 4273 CB GLU B 281 54 .152 3.848 34 .719 1 .00 47 .41 6

ATOM 4274 CG GLU B 281 54 .308 2.918 33 .516 1 .00 48 .19 6

ATOM 4275 CD GLU B 281 53 .705 3.562 32 .275 1 .00 50 .10 6

ATOM 4276 OE1 GLU B 281 52 .718 4.312 32 .460 1 .00 51 .21 8

ATOM 4277 OE2 GLU B 281 54 .203 3.330 31 .153 1 .00 50 .72 8

ATOM 4278 N LEU B 282 54 .358 7.077 35 .662 1 .00 49 .43 7

ATOM 4279 CA LEU B 282 54 .144 8.043 36 .731 1 .00 52 .69 6

ATOM 4280 C LEU B 282 52 .714 8.211 37 .222 1 .00 56 .10 6

ATOM 4281 O LEU B 282 51 .741 8.259 36 .479 1 .00 57 .86 8

ATOM 4282 CB LEU B 282 54 .654 9.413 36 .232 1 .00 51 .33 6

ATOM 4283 CG LEU B 282 56 .153 9.442 35 .898 1 . 00 51 .16 6

ATOM 4284 CDl LEU B 282 56 .568 10.774 35 .313 1 .00 49 .90 6

ATOM 4285 CD2 LEU B 282 56 .959 9.109 37 .146 1 . 00 50 .87 6

ATOM 4286 N ALA B 283 52 .591 8.404 38 .527 1 .00 58 .60 7

ATOM 4287 CA ALA B 283 51 .340 8.572 39 .260 1 .00 61 .51 6

ATOM 4288 C ALA B 283 50 .222 7.659 38 .748 1 .00 62 .69 6

ATOM 4289 O ALA B 283 49 .365 7.240 39 .565 1 .00 64 .21 8

ATOM 4290 CB ALA B 283 50 .878 10.031 39 .215 1 .00 61 .28

Water

Atom Occ . -J en en cπ Ul j-» d-> CO CO t to H> o Ul o Ul σ αi σ cπ o cπ σ Ul o cπ

r_ ι-_ H ι-_ r_ ι-_ r_ H H H >-- ^ r_ H r_ h r_ H ι-_ ι-- r_ H r_ H H ι-- ^ ^ ι-- r_ r_ H H H r_ H >-_ ^ oooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooo gggggggggggggggggggggggggggggggggggggggggggggggggggggggggggggggggggggggg

ωcoωωcoωωcoωωωωcocococoωcocυωcυωcoωωcoωωcocoωcoω

-j^-j^^c onc cnmc cncncnc cπcπcjiϋicncπuicπcπcnj-.--.--,--.-^-^-^

--.co MθcDCo^cΛW-^ωMMocDαD-Jcnw*.ω Mθ D∞^σ\ϋι-:-CJ Mθ oco^cnoι-^ oooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooo - sasasg aasaaaaassssasssaaa-issgassssasiaass-isssggsasssasssassgasassassssssis 3 ^ H r3 r_ 3 r_ H3 ι-3 ι-3 β 3 μ. 3 r3 ^ 3 . H3 H. 3 r3 h-g ι-3 ^ 3 ^ 3 r3 H ι-3 . ^ ι^ H3 ι-3 ι-3 a ^ ^ ι-3 ι-3 ι-3 ^ asaaaaaassaaaaaa !SSSS3SSSS3SSSSa333Sl ggss;ssasssss;ss3s;s;sgssss!sas3ss!ss:ss;sss;sι

-J^-Jσ cnσϊθncncΛcnc cnc cjιoιuιcπcπcπcπuισιcπ--.-^-^-^d^-^-^ t θlDffi J(Jl Jl~. Jt θtOOθ !σiCn(E.ϋWμθ«3(D- c π -^ωMMOCDCO-JcnCπ-_.COMMOCOCO-J l π--. )MM COCO_^JcnCrι-_. CO_'M MOCDCO-OCnCπ~-. >M

cnσ\cnc σ ω--.-^ωM-^ωj^cn-j-_.α Cι-^cπωuιcnω--.--.--.ω mcπ COC^ClMcn OClCOCOM^ CAJOMO O -^ I-^OO-J lOϋlM D-^OOnMM-JCDωcnCO -JCπ-^MMMO -^

(n iΔHωμto iWμowffiWu ioiμωJt μiDm^ooinΛcoujiDcoifiMMetiωwμω iμωoiωivt i- CD.M McoσιMMσ>MMθcocπcoocoj-. MMocDcocD )MMMCO-^C^OMD^OMCDσ^-^CnOCΛMCOMCOOΛ^MC M -J-^MM CπM-40COO^O-^C OCD ^MMMωσι-^CπcnOO-^ co^^ocπc co--.^co^ocn-^o MCπcυcDcnMcoM-^Mooωcnococncoσ -^-^-^ M-^ ocnC7icnMMCoω l l l l l I I I I

I M I MMMM M MMMM I MM I MMM I MMM I MMMM I I I I M MMMMMM I M M MM I MMMM MM MMM I I MM

*-.uμμiΛθN» μuoωωuouJU imojμM jooιμtJtJuιooιuμ»ωooBθi NtjMμMUt ϊ) (jιoιuco(iιϋιiBiιιiD πoooocnμμuJ cβtπΛUO πJMϋw^t cDNi^ω^-.CDWuu-.^^μwLπμcooϋ^^ i-'ώω jtjTowμo^oMr.^oμoω^-.ocot-o^iDo^^om ωtAj ffl

CDMMCDCnM^CDC0CJlθωθCJ1O-4C0C0OCDO-^CnCn--J-4mOCDC0C0MMCJICnC0C0MCΛjCD--JC0CJlCDCjπCJ1CDOM ωCΛCπM^cπ DCDcoco >-^coω^--.cnwM-JMc c ^o^Mco^ DMω-J -J^-^M--JM--.MM co

I I I l l l l I I l l l l

MC0MM 1 I MM M M M M I CO I I MMMM I MM MMMMM M I I J-. I I M I I MMMMMM I MM I t-> t-¹ MM M I M I M M

-Jω DO MωOCO^∞M OCDDC^jiω^-^OO∞oωCπCJ^l C^jicn-^∞^-JO OCπCπ -ⁱ-^-^M-^MCn

C0CπC0C0ωoωCπθ-JMM-^OOC0CD--.e^MC0MC0OT^OcnωMM0nCπθC0MMC0OC0OMJ-.MC0CDOCDM-^-JMM--JM0lC^ Mc oiMcncπ ^Cj Mc couiocΛωoM D-^-^oω Cococo D -^ -^ω-^cπoono cnco-^ o-^ω

COM-^OMmMCjπMσiCDMMCnCD-^O-^CJlMMCDCOMωMUIOlMσ^CπCOCOUlMMM^COCriCDCOMCOMDM-JCnMCnMOOω

M M M M M M M M I 'MMMMMMMMMMMI 'MMMMMMMMMMMMMMMMMMMl ' t-' V^ t-' t-' t-' t-' -' l-' f-' t-' t-' t-' t-' t-' t-' t-' l-' ooooooooooooooooooooooooooooooσoooooooooσooooαooooσooooooooooooooooooooo σooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooo

MCOMMωω-^C0MC0C0C0MMMMC0ωWMMC0MωMMωωω-^COMC0MMMωMMC --.MMMC0MMMC0ωMMMMMM-iMMMMMMMMMMMωMM

-i--j^α3ω-^MMCDθ--JMCDcocooncoMω-^CιωcπcncDM--.MCDσιcocoooDco--4ocncncnω

^DCji-^CDMCjicn--.coCA)o^coa^Mtji^ nco oocncnMO(nM it^oon-^(ji- cncji-^c c^ ∞CJicn^cncD~^CDθco o--. Cjι ncocjιcnθMcxι-JM-^MθJ cDcno--.o o --JMM C cocD-J-^ocD»^

-J en en Ul Ul d-- -&. co co to t o cπ o Ul o Cπ o Ui O Cπ o Ul o Ul

HH 3 3 _H-^μ-H. .Hι-3H - - .^μ-r3r3rtHι^ 3ι--H.H3r3ι-3r3^μ3r3 3r3H.^μ.H3ι-3Hr3ιH3H 3HH 3

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co-^cπcncπ-^ωCΛ}Cjισϊ-^o^ j-.cnM Cπcπ,----. c ωωuι-4-^cπc cπω M-^cjι-^.t_*cDM--.-^cncoM-^cπ-^.ι^σ ow-^CΛ -J.--cnGj-4c Mσ^coco-^

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MM cooocncD oo D-^cπMθCocD Dθico-jcπoco--. iMc oMcnCΛ)--Jθcπc --JcnM^σιθMUJcπ DCoc -Jo^ ^αD^-4^coc cσ n-^Mcocn-^ πcoco^ cocnouj^ υ^ -^~^-^-^-^uιcnco oωc^

ATOM 4449 O WAT W 147 65.891 12.184 46.900 1.00 41.27

ATOM 4450 O WAT W 148 61.870 -0.694 32.618 1.00 36.54

ATOM 4451 O WAT W 149 53.665 -22.423 14.114 1.00 45.13

ATOM 4452 O WAT W 150 70.406 -11.509 9.153 1.00 39.16

ATOM 4453 O WAT W 151 57.272 24.770 -5.465 1.00 53.97

ATOM 4454 O WAT W 152 76.932 13.052 43.714 1.00 34.28

ATOM 4455 O WAT W 153 46.722 -10.271 21.629 1.00 39.60

ATOM 4456 O WAT W 154 71.871 -14.779 14.884 1.00 41.12

ATOM 4457 O WAT W 155 75.221 -2.490 33.675 1.00 36.01

ATOM 4458 O WAT W 156 79.538 8.216 41.312 1.00 39.15

ATOM 4459 O WAT W 157 37.416 -3.706 5.762 1.00 38.40

ATOM 4460 O WAT W 158 35.517 15.310 19.620 1.00 36.39

ATOM 4461 O WAT W 159 51.237 5.731 5.785 1.00 34.79

ATOM 4462 O WAT W 160 51.381 -1.632 26.211 1.00 44.45

ATOM 4463 O WAT W 161 43.466 16.232 -32.007 1.00 52.60

ATOM 4464 O WAT W 162 75.662 12.257 40.222 1.00 38.37

ATOM 4465 O WAT W 163 32.057 -13.026 10.708 1.00 39.45

ATOM 4466 O WAT W 164 44.346 0.072 6.468 1.00 36.40

ATOM 4467 O WAT W 165 52.324 -2.560 -1.704 1.00 46.60

ATOM 4468 O WAT W 166 57.861 8.649 -15.458 1.00 41.61

ATOM 4469 O WAT W 167 67.132 -5.044 15.257 1.00 40.23

ATOM 4470 O WAT W 168 59.264 -1.197 31.588 1.00 51.30

ATOM 4471 O WAT W 169 51.835 3.346 23.021 1.00 39.67

ATOM 4472 0 WAT W 170 57.419 -5.177 -4.443 1.00 35.72

ATOM 4473 0 WAT W 171 48.627 11.775 20.770 1.00 47.02

ATOM 4474 0 WAT W 172 64.778 -5.263 25.321 1.00 34.04

ATOM 4475 0 WAT W 173 21.644 11.926 -2.423 1.00 35.54

ATOM 4476 0 WAT W 174 40.345 0.581 13.671 1.00 59.11

ATOM 4477 0 WAT W 175 65.019 -5.440 32.798 1.00 40.87

ATOM 4478 0 WAT W 176 44.228 -7.202 4.474 1.00 39.61

ATOM 4479 0 WAT W 177 83.719 10.000 40.277 1.00 42.80

ATOM 4480 0 WAT W 178 68.408 -7.591 -0.478 1.00 38.18

ATOM 4481 0 WAT W 179 63.973 -9.992 -4.755 1.00 51.42

ATOM 4482 0 WAT W 180 39.726 7.902 -27.189 1.00 49.92

ATOM 4483 0 WAT W 181 55.044 0.850 -6.811 1.00 51.09

ATOM 4484 0 WAT W 182 25.424 1.610 -6.315 1.00 30.30

ATOM 4485 0 WAT W 183 25.655 20.392 -3.870 1.00 43.57

ATOM 4486 0 WAT W 184 43.760 -10.333 15.054 1.00 39.92

ATOM 4487 0 WAT W 185 46.383 19.180 -9.597 1.00 33.30

ATOM 4488 0 WAT W 186 57.924 9.404 -18.120 1.00 44.22

ATOM 4489 0 WAT W 187 58.234 -16.451 0.308 1.00 36.17

ATOM 4490 0 WAT W 188 38.059 -19.859 11.817 1.00 32.02

ATOM 4491 0 WAT W 189 42.349 23.603 0.069 1.00 55.22

ATOM 4492 0 WAT W 190 62.117 0.301 41.059 1.00 47.46

ATOM 4493 0 WAT W 191 39.146 34.096 6.333 1.00 35.61

ATOM 4494 0 WAT W 192 52.021 -17.641 1.723 1.00 36.52

ATOM 4495 0 WAT W 193 30.405 15.315 -12.140 1.00 40.90

ATOM 4496 0 WAT W 194 56.589 6.376 -25.137 1.00 50.29

ATOM 4497 0 WAT W 195 32.292 21.747 -31.418 1.00 30.10

ATOM 4498 0 WAT W 196 25.932 26.262 -31.876 1.00 33.19

ATOM 4499 0 WAT W 197 44.253 27.169 0.607 1.00 41.25

ATOM 4500 0 WAT W 198 31.985 18.702 10.898 1.00 43.36

ATOM 4501 0 WAT W 199 66.104 14.551 9.666 1.00 42.15

ATOM 4502 0 WAT W 200 65.400 14.447 48.384 1.00 54.11

ATOM 4503 0 WAT W 201 23.164 26.745 -32.350 1.00 43.78

ATOM 4504 0 WAT W 202 36.449 -19.529 9.775 1.00 56.52

ATOM 4505 0 WAT W 203 37.955 9.830 -30.717 1.00 42.18

ATOM 4506 0 WAT W 204 80.612 -6.612 30.354 1.00 58.09

ATOM 4507 0 WAT W 205 42.193 -5.177 3.641 1.00 53.40

ATOM 4508 0 WAT W 206 34.846 19.253 -0.441 1.00 43.51

ATOM 4509 0 WAT W 207 55.615 -2.982 -4.231 1.00 46.41

ATOM 4510 0 WAT W 208 51.625 4.220 -8.519 1.00 45.10

ATOM 4511 0 WAT W 209 25.739 8.524 -24.942 1.00 36.13

ATOM 4512 0 WAT W 210 68.747 17.314 21.066 1.00 43.56

ATOM 4513 0 WAT W 211 84.666 3.989 47.339 1.00 56.35

ATOM 4514 0 WAT W 212 39.125 28.472 0.851 1.00 43.49

ATOM 4515 0 WAT W 213 40.758 -6.436 1.126 1.00 43.08

ATOM 4516 0 WAT W 214 65.742 -7.673 25.260 1.00 39.84

ATOM 4517 0 WAT W 215 68.113 -7.014 26.268 1.00 44.06

ATOM 4518 0 WAT W 216 50.292 24.666 -37.803 1.00 47.27

ATOM 4519 0 WAT W 217 76.215 -4.709 32.421 1.00 35.98

ATOM 4520 0 WAT W 218 28.732 31.945 -22.056 1.00 33.29

ATOM 4521 0 WAT W 219 74.218 14.100 34.912 1.00 76.11

ATOM 4522 0 WAT W 220 57.961 0.451 28.074 1.00 47.45 -J en en Ul Ul d-» LO CO to N3 o Ul o UI o Ul o Ul O cπ o π O Ul

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ATOM 4671 O WAT W 369 88..460 -12..813 38.,004 1..00 20.,00

ATOM 4672 O WAT W 370 91. .761 -9. .669 35. .928 1. .00 20. ,00

ATOM 4673 O WAT W 371 88. ,580 -15. ,367 38. .475 1. .00 20. ,00

ATOM 4674 O WAT W 372 76. .861 -9. .543 44, .348 1. .00 20. .00

ATOM 4675 O WAT W 373 74. .471 -6. .743 45, .210 1. .00 20. .00

ATOM 4676 O WAT W 374 79. .402 -2. .424 46, .754 1. .00 20. .00

ATOM 4677 O WAT W 375 75. .647 -0. .122 49, .778 1. .00 20. .00

ATOM 4678 O WAT W 376 77, .752 1. .584 49, .411 1, .00 20. .00

ATOM 4679 O WAT W 377 37, .468 -4, .589 21 .373 1, .00 20, .00

ATOM 4680 O WAT W 378 45. .334 -7, .735 21 .716 1. .00 20, .00

ATOM 4681 O WAT W 379 46, .136 -5, .299 22 .588 1, .00 20. .00

ATOM 4682 O WAT W 380 43, .144 -7, .232 20 .423 1, .00 20, ,00

ATOM 4683 O WAT W 381 42 .129 -4, .775 20 .988 1. .00 20, .00

ATOM 4684 O WAT W 382 47 .659 -14 .000 24 .499 1 .00 20, .00

ATOM 4685 O WAT W 383 41 .892 -6, .834 15 .632 1 .00 20, .00

ATOM 4686 O WAT W 384 42 .961 -8 .398 13 .868 1 .00 20 .00

Table 2

Composition of defined minimal culture medium for selenium-containing PS. All components were filter- sterilized through 0.22μm filters, except where indicated.

' Sambrook, J., Fritsch, E. F. & Maniatis, T. (1989). Molecular cloning: a laboratory manual, 2nd ed. Cold Spring Harbour Laboratory Press, Cold Spring Harbor, N.Y. Table 3

Cry stallo graphic refinement

No reflexions (test set) 11 294 (4062) Test set is excluded from refinement for cross-validation

No restraints 15730 Restraints in TNT with a weight assigned

No parameters 20236

Weight for geom restraints (TNT) 3

Final model parameters

Residues 566

Hetero 1 Tπs, 2 ethanediol

No water molecules 622

No non-hydrogen atoms 5059

Resolution range (A) 45 - 1 7

Refinement convergence

^■ftfree 249 R_fxw calculated using test reflexions tH-uor 22 6 β|-_αor = ∑_hUF„_bsi - !F-_a| I / Σ_hIF„_b.l, w/o test reflexions

DDQ (score, ranking) UFO 071 (bottom 25%) "Unassigned positive Feature left-Over score"

DDQ-R 15 2 (bottom 25%) Ratio of Shift and Water peak contributions

Average β-factor, subunit A (A²) 33 9 subunit B (A²) 36 4 waters (A²) 47 8

Wilson distribution β_rjUor (A²) 28 0

Model quality

Ramachandran plot % residues in most favoured region 922

% residues in generously-allowed region 7 4

No residues in disallowed region 0

Rms deviation from ideal Covalent bond lengths (A) 0 018 ("root mean square") Bond angles (°) 1 41

Planar groups (A) 0 007

Procheck catena % bond lengths outside expected limits 2 6

% bond angles outside expected limits 3 1

% planar groups outside expected limits 1 0 WhatCheck criteria No unsaturated H-bonds 2

No residues in unusual environments 14 _^J i CTl i cπ >t- j-» cυ cυ t N> -¹ o cπ o αi o cπ o cπ o αi o Cπ o cπ

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Claims

Clalms :

1. A crystal of pantothenate synthetase (PS) having a monoclinic space group P2χ and unit cell dimensions of a = 66.0+0.2A, b = 78.1±0.2A, c = 77.liO.2A and β = 103.7+0.2°.

2. A crystal of PS having the three dimensional atomic coordinates of Table 1 .

3. A method for crystallizing a selenium atom PS derivative which comprises producing PS by recombinant production in a bacterial host in the presence of selenomethionine, recovering a selenium atom PS derivative from the host and growing crystals from the recovered selenium atom PS derivative.

4. A computer-based method of rational drug design which comprises : providing the structure of the PS as defined by the coordinates of Table 1; providing the structure of a candidate modulator molecule; and fitting the structure of the candidate modulator molecule to the structure of the PS of Table 1.

5. A computer-based method of rational drug design which comprises : providing the coordinates of at least two atoms of the PS of Table 1; providing the structure of a candidate modulator molecule; and fitting the structure of the candidate modulator molecule to the provided coordinates of the PS.

6. A computer-based method of rational drug design which comprises: providing the coordinates of at least a sub-domain of the PS; providing the structure of a candidate modulator molecule; and fitting the structure of the candidate modulator molecule to the coordinates of the PS sub-domain provided.

7. The method of any one of claims 4 to 6 which further comprises the steps of: obtaining or synthesising the candidate modulator; and contacting the candidate modulator with PS to determine the ability of the candidate modulator to interact with PS.

8. The method of any one of claims 4 to 6 which further comprises the steps of: obtaining or synthesising said candidate modulator; forming a complex of PS and said potential modulator; and analysing said complex by X-ray crystallography to determine the ability of said candidate modulator to interact with PS.

9. A compound having a chemical structure selected using the method of any one of claims 4 to 6, said compound being an inhibitor of PS.

10. A computer readable medium with either (a) atomic data according to Table 1 recorded thereon, said data defining the three-dimensional structure of PS or at least one sub-domain thereof or (b) structure factor data for PS recorded thereon, the structure factor data being derivable from the atomic coordinate data of Table 1.

11. A computer system, intended to generate structures and/or perform rational drug design for PS or complexes of PS with a potential modulator, the system containing either (a) atomic coordinate data according to Table 1, said data defining the three-dimensional structure of PS or at least one sub-domain thereof or (b) structure factor data for PS, said structure factor data being derivable from the atomic coordinate data of Table 1.